DNA damage and the balance between survival and death in cancer biology (original) (raw)
Voulgaridou, G. P., Anestopoulos, I., Franco, R., Panayiotidis, M. I. & Pappa, A. DNA damage induced by endogenous aldehydes: current state of knowledge. Mutat. Res.711, 13–27 (2011). ArticleCASPubMed Google Scholar
Fialkow, L., Wang, Y. & Downey, G. P. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic. Biol. Med.42, 153–164 (2007). ArticleCASPubMed Google Scholar
Kielbassa, C., Roza, L. & Epe, B. Wavelength dependence of oxidative DNA damage induced by UV and visible light. Carcinogenesis18, 811–816 (1997). ArticleCASPubMed Google Scholar
Cadet, J., Ravanat, J. L., TavernaPorro, M., Menoni, H. & Angelov, D. Oxidatively generated complex DNA damage: tandem and clustered lesions. Cancer Lett.327, 5–15 (2012). ArticleCASPubMed Google Scholar
Roos, W. P. & Kaina, B. DNA damage-induced cell death: from specific DNA lesions to the DNA damage response and apoptosis. Cancer Lett.332, 237–248 (2013). ArticleCASPubMed Google Scholar
Fulda, S. Cell death and survival signaling in oncogenesis. Klin. Padiatr.222, 340–344 (2010). ArticleCASPubMed Google Scholar
Helleday, T., Petermann, E., Lundin, C., Hodgson, B. & Sharma, R. A. DNA repair pathways as targets for cancer therapy. Nat. Rev. Cancer8, 193–204 (2008). ArticleCASPubMed Google Scholar
Fu, D., Calvo, J. A. & Samson, L. D. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat. Rev. Cancer12, 104–120 (2012). ArticleCASPubMedPubMed Central Google Scholar
Kaina, B., Christmann, M., Naumann, S. & Roos, W. P. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst.)6, 1079–1099 (2007). ArticleCAS Google Scholar
Ensminger, M. et al. DNA breaks and chromosomal aberrations arise when replication meets base excision repair. J. Cell Biol.206, 29–43 (2014). ArticleCASPubMedPubMed Central Google Scholar
Halazonetis, T. D., Gorgoulis, V. G. & Bartek, J. An oncogene-induced DNA damage model for cancer development. Science319, 1352–1355 (2008). ArticleCASPubMed Google Scholar
Ando, K. et al. PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling. Mol. Cell47, 681–693 (2012). ArticleCASPubMedPubMed Central Google Scholar
Lips, J. & Kaina, B. DNA double-strand breaks trigger apoptosis in p53-deficient fibroblasts. Carcinogenesis22, 579–585 (2001). ArticleCASPubMed Google Scholar
Virag, L., Robaszkiewicz, A., Rodriguez-Vargas, J. M. & Oliver, F. J. Poly(ADP-ribose) signaling in cell death. Mol. Aspects Med.34, 1153–1167 (2013). ArticleCASPubMed Google Scholar
Chiu, L. Y., Ho, F. M., Shiah, S. G., Chang, Y. & Lin, W. W. Oxidative stress initiates DNA damager MNNG-induced poly(ADP-ribose)polymerase-1-dependent parthanatos cell death. Biochem. Pharmacol.81, 459–470 (2011). ArticleCASPubMed Google Scholar
Zhou, Z. D., Chan, C. H., Xiao, Z. C. & Tan, E. K. Ring finger protein 146/Iduna is a poly(ADP-ribose) polymer binding and PARsylation dependent E3 ubiquitin ligase. Cell Adh. Migr.5, 463–471 (2011). ArticlePubMedPubMed Central Google Scholar
Roos, W. P. et al. The translesion polymerase Rev3L in the tolerance of alkylating anticancer drugs. Mol. Pharmacol.76, 927–934 (2009). ArticleCASPubMed Google Scholar
Ashour, M. E., Atteya, R. & El-Khamisy, S. F. Topoisomerase-mediated chromosomal break repair: an emerging player in many games. Nat. Rev. Cancer15, 137–151 (2015). ArticleCASPubMed Google Scholar
Stingele, J., Habermann, B. & Jentsch, S. DNA–protein crosslink repair: proteases as DNA repair enzymes. Trends Biochem. Sci.40, 67–71 (2015). ArticleCASPubMed Google Scholar
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S. & Bonner, W. M. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem.273, 5858–5868 (1998). Identification of a specific marker of DSBs, namely, the phosphorylated form of H2AX (γH2AX), greatly stimulated research on DNA damage.γH2AX is currently the most sensitive marker for DSBs and blocked replication forks. ArticleCASPubMed Google Scholar
Eich, M., Roos, W. P., Nikolova, T. & Kaina, B. Contribution of ATM and ATR to the resistance of glioblastoma and malignant melanoma cells to the methylating anticancer drug temozolomide. Mol. Cancer Ther.12, 2529–2540 (2013). ArticleCASPubMed Google Scholar
Stankovic, T. et al. ATM mutations in sporadic lymphoid tumours. Leuk. Lymphoma43, 1563–1571 (2002). ArticleCASPubMed Google Scholar
Kim, H. et al. Having pancreatic cancer with tumoral loss of ATM and normal TP53 protein expression is associated with a poorer prognosis. Clin. Cancer Res.20, 1865–1872 (2014). ArticleCASPubMedPubMed Central Google Scholar
Pusapati, R. V. et al. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Proc. Natl Acad. Sci. USA103, 1446–1451 (2006). ArticleCASPubMedPubMed Central Google Scholar
Bitomsky, N. & Hofmann, T. G. Apoptosis and autophagy: regulation of apoptosis by DNA damage signalling — roles of p53, 73 and HIPK2. FEBS J.276, 6074–6083 (2009). ArticleCASPubMed Google Scholar
Dahal, G. R. et al. Caspase-2 cleaves DNA fragmentation factor (DFF45)/inhibitor of caspase-activated DNase (ICAD). Arch. Biochem. Biophys.468, 134–139 (2007). Here, the authors demonstrated a direct link between nuclear caspase 2 and the apoptosis-triggering nuclease CAD. ArticleCASPubMed Google Scholar
Bernstein, C., Bernstein, H., Payne, C. M. & Garewal, H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat. Res.511, 145–178 (2002). ArticleCASPubMed Google Scholar
Xu, Y. & Baltimore, D. Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes Dev.10, 2401–2410 (1996). In this paper it is shown, usingAtm-knockout mice, that ATM plays a role in the DDR to ionizing radiation. ArticleCASPubMed Google Scholar
Swift, M., Morrell, D., Massey, R. B. & Chase, C. L. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N. Engl. J. Med.325, 1831–1836 (1991). ArticleCASPubMed Google Scholar
Thompson, D. et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J. Natl Cancer Inst.97, 813–822 (2005). ArticleCASPubMed Google Scholar
Tanaka, A. et al. Germline mutation in ATR in autosomal- dominant oropharyngeal cancer syndrome. Am. J. Hum. Genet.90, 511–517 (2012). In references 35–37, evidence is provided that mutations inATMandATRcan predispose to cancer development. ArticleCASPubMedPubMed Central Google Scholar
Khanna, K. K. Cancer risk and the ATM gene: a continuing debate. J. Natl Cancer Inst.92, 795–802 (2000). ArticleCASPubMed Google Scholar
Galluzzi, L., Vitale, I., Vacchelli, E. & Kroemer, G. Cell death signaling and anticancer therapy. Front. Oncol.1, 5 (2011). PubMedPubMed Central Google Scholar
Helleday, T. Homologous recombination in cancer development, treatment and development of drug resistance. Carcinogenesis31, 955–960 (2010). ArticleCASPubMed Google Scholar
Sale, J. E. Competition, collaboration and coordination—determining how cells bypass DNA damage. J. Cell Sci.125, 1633–1643 (2012). CASPubMed Google Scholar
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T. & Kroemer, G. Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat. Rev. Mol. Cell Biol.11, 700–714 (2010). ArticleCASPubMed Google Scholar
Bartek, J. & Lukas, J. DNA damage checkpoints: from initiation to recovery or adaptation. Curr. Opin. Cell Biol.19, 238–245 (2007). ArticleCASPubMed Google Scholar
Vakifahmetoglu, H., Olsson, M. & Zhivotovsky, B. Death through a tragedy: mitotic catastrophe. Cell Death Differ.15, 1153–1162 (2008). ArticleCASPubMed Google Scholar
Lahav, G. et al. Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat. Genet.36, 147–150 (2004). ArticleCASPubMed Google Scholar
Zhang, X. P., Liu, F., Cheng, Z. & Wang, W. Cell fate decision mediated by p53 pulses. Proc. Natl Acad. Sci. USA106, 12245–12250 (2009). ArticleCASPubMedPubMed Central Google Scholar
Tian, X. J., Liu, F., Zhang, X. P., Li, J. & Wang, W. A two-step mechanism for cell fate decision by coordination of nuclear and mitochondrial p53 activities. PLoS ONE7, e38164 (2012). ArticleCASPubMedPubMed Central Google Scholar
Inga, A., Storici, F., Darden, T. A. & Resnick, M. A. Differential transactivation by the p53 transcription factor is highly dependent on p53 level and promoter target sequence. Mol. Cell. Biol.22, 8612–8625 (2002). The differential binding affinity of p53 for target promoters and its contribution to the different functions of p53 was demonstrated in this work. ArticleCASPubMedPubMed Central Google Scholar
Nicol, S. M. et al. The RNA helicase p68 (DDX5) is selectively required for the induction of p53-dependent p21 expression and cell-cycle arrest after DNA damage. Oncogene32, 3461–3469 (2013). ArticleCASPubMed Google Scholar
Tanaka, T. Ohkubo, S., Tatsuno, I. & Prives, C. hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes. Cell130, 638–650 (2007). ArticleCASPubMed Google Scholar
Lettre, G. et al. Genome-wide RNAi identifies p53-dependent and -independent regulators of germ cell apoptosis in C. elegans. Cell Death Differ.11, 1198–1203 (2004). ArticleCASPubMed Google Scholar
Loughery, J., Cox, M., Smith, L. M. & Meek, D. W. Critical role for p53-serine 15 phosphorylation in stimulating transactivation at p53-responsive promoters. Nucleic Acids Res.42, 7666–7680 (2014). ArticleCASPubMedPubMed Central Google Scholar
Jabbur, J. R., Huang, P. & Zhang, W. DNA damage-induced phosphorylation of p53 at serine 20 correlates with p21 and Mdm-2 induction in vivo. Oncogene19, 6203–6208 (2000). References 53 and 54 show that p53 phosphorylated at Ser15 and Ser20 displays different roles in auto-regulation and cell cycle checkpoint activation. ArticleCASPubMed Google Scholar
Ichwan, S. J. et al. Defect in serine 46 phosphorylation of p53 contributes to acquisition of p53 resistance in oral squamous cell carcinoma cells. Oncogene25, 1216–1224 (2006). ArticleCASPubMed Google Scholar
Mayo, L. D. et al. Phosphorylation of human p53 at serine 46 determines promoter selection and whether apoptosis is attenuated or amplified. J. Biol. Chem.280, 25953–25959 (2005). In this paper it is shown that p53 phosphorylated at Ser46 specifically activates pro-apoptotic genes. ArticleCASPubMed Google Scholar
Oda, K. et al. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell102, 849–862 (2000). ArticleCASPubMed Google Scholar
Hofmann, T. G. et al. Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat. Cell Biol.4, 1–10 (2002). In this paper, it is shown for the first time that HIPK2 is responsible for phosphorylating p53 at Ser46 in response to DNA damage. ArticleCASPubMed Google Scholar
Bulavin, D. V. et al. Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J.18, 6845–6854 (1999). ArticleCASPubMedPubMed Central Google Scholar
Yoshida, K., Liu, H. & Miki, Y. Protein kinase Cδ regulates Ser46 phosphorylation of p53 tumor suppressor in the apoptotic response to DNA damage. J. Biol. Chem.281, 5734–5740 (2006). ArticleCASPubMed Google Scholar
Okamura, S. et al. p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis. Mol. Cell8, 85–94 (2001). ArticleCASPubMed Google Scholar
Taira, N., Nihira, K., Yamaguchi, T., Miki, Y. & Yoshida, K. DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage. Mol. Cell25, 725–738 (2007). ArticleCASPubMed Google Scholar
Lee, M. G. et al. XAF1 directs apoptotic switch of p53 signaling through activation of HIPK2 and ZNF313. Proc. Natl Acad. Sci. USA111, 15532–15537 (2014). ArticleCASPubMedPubMed Central Google Scholar
Winter, M. et al. Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. Nat. Cell Biol.10, 812–824 (2008). This paper shows that HIPK2 is part of the DDR. ArticleCASPubMed Google Scholar
Guo, A. et al. The function of PML in p53-dependent apoptosis. Nat. Cell Biol.2, 730–736 (2000). ArticleCASPubMed Google Scholar
Takekawa, M. et al. p53-inducible Wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J.19, 6517–6526 (2000). ArticleCASPubMedPubMed Central Google Scholar
Zhao, S. et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1α. Science324, 261–265 (2009). ArticleCASPubMedPubMed Central Google Scholar
Bulavin, D. V. et al. Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat. Genet.31, 210–215 (2002). ArticleCASPubMed Google Scholar
Tamm, I. et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res.58, 5315–5320 (1998). CASPubMed Google Scholar
Ambrosini, G., Adida, C. & Altieri, D. C. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat. Med.3, 917–921 (1997). Here, it was demonstrated that survivin, which was thought to only have a role during fetal development, is overexpressed in tumours, having a role in apoptosis regulation. ArticleCASPubMed Google Scholar
Knauer, S. K., Mahendrarajah, N., Roos, W. P. & Kramer, O. H. The inducible E3 ubiquitin ligases SIAH1 and SIAH2 perform critical roles in breast and prostate cancers. Cytokine Growth Factor Rev.26, 405–413 (2015). ArticleCASPubMed Google Scholar
De Carvalho, D. D. et al. DNA methylation screening identifies driver epigenetic events of cancer cell survival. Cancer Cell21, 655–667 (2012). ArticleCASPubMedPubMed Central Google Scholar
Ljungman, M. & Lane, D. P. Transcription — guarding the genome by sensing DNA damage. Nat. Rev. Cancer4, 727–737 (2004). ArticleCASPubMed Google Scholar
Derheimer, F. A. et al. RPA and ATR link transcriptional stress to p53. Proc. Natl Acad. Sci. USA104, 12778–12783 (2007). This paper showed convincingly that DNA lesions blocking transcription activate ATR and consequently the DDR. ArticleCASPubMedPubMed Central Google Scholar
Conforti, G., Nardo, T., D'Incalci, M. & Stefanini, M. Proneness to UV-induced apoptosis in human fibroblasts defective in transcription coupled repair is associated with the lack of Mdm2 transactivation. Oncogene19, 2714–2720 (2000). ArticleCASPubMed Google Scholar
Hwang, B. J., Ford, J. M., Hanawalt, P. C. & Chu, G. Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc. Natl Acad. Sci. USA96, 424–428 (1999). ArticleCASPubMedPubMed Central Google Scholar
Barckhausen, C., Roos, W. P., Naumann, S. C. & Kaina, B. Malignant melanoma cells acquire resistance to DNA interstrand cross-linking chemotherapeutics by p53-triggered upregulation of DDB2/XPC-mediated DNA repair. Oncogene33, 1964–1974 (2014). ArticleCASPubMed Google Scholar
Batista, L. F., Roos, W. P., Christmann, M., Menck, C. F. & Kaina, B. Differential sensitivity of malignant glioma cells to methylating and chloroethylating anticancer drugs: 53 determines the switch by regulating xpc, ddb2, and DNA double-strand breaks. Cancer Res.67, 11886–11895 (2007). Here, the dependence on the anticancer drug to activate the dual function of p53 in regulating apoptosis or DNA repair is demonstrated. ArticleCASPubMed Google Scholar
Proietti De Santis, L. et al. Transcription coupled repair efficiency determines the cell cycle progression and apoptosis after UV exposure in hamster cells. DNA Repair (Amst.)1, 209–223 (2002). Article Google Scholar
Ljungman, M., O'Hagan, H. M. & Paulsen, M. T. Induction of ser15 and lys382 modifications of p53 by blockage of transcription elongation. Oncogene20, 5964–5971 (2001). ArticleCASPubMed Google Scholar
Herrlich, P. et al. The mammalian UV response: mechanism of DNA damage induced gene expression. Adv. Enzyme Regul.34, 381–395 (1994). ArticleCASPubMed Google Scholar
Tomicic, M. T. et al. Delayed c-Fos activation in human cells triggers XPF induction and an adaptive response to UVC-induced DNA damage and cytotoxicity. Cell. Mol. Life Sci.68, 1785–1798 (2011). ArticleCASPubMed Google Scholar
Haas, S. & Kaina, B. c-Fos is involved in the cellular defence against the genotoxic effect of UV radiation. Carcinogenesis16, 985–991 (1995). ArticleCASPubMed Google Scholar
Kaina, B., Haas, S. & Kappes, H. A general role for c-Fos in cellular protection against DNA-damaging carcinogens and cytostatic drugs. Cancer Res.57, 2721–2731 (1997). CASPubMed Google Scholar
Christmann, M., Tomicic, M. T., Origer, J., Aasland, D. & Kaina, B. c-Fos is required for excision repair of UV-light induced DNA lesions by triggering the re-synthesis of XPF. Nucleic Acids Res.34, 6530–6539 (2006). In references 86–89, evidence is provided that FOS has a dual role in regulating DNA repair and, if repair is saturated, apoptosis. ArticleCASPubMedPubMed Central Google Scholar
Christmann, M. & Kaina, B. Transcriptional regulation of human DNA repair genes following genotoxic stress: trigger mechanisms, inducible responses and genotoxic adaptation. Nucleic Acids Res.41, 8403–8420 (2013). ArticleCASPubMedPubMed Central Google Scholar
Marteijn, J. A., Lans, H., Vermeulen, W. & Hoeijmakers, J. H. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol.15, 465–481 (2014). ArticleCASPubMed Google Scholar
Hamdi, M. et al. DNA damage in transcribed genes induces apoptosis via the JNK pathway and the JNK-phosphatase MKP-1. Oncogene24, 7135–7144 (2005). The fundamental relationship between NER, JNK, MKP1 and apoptosis was elucidated in this article. ArticleCASPubMed Google Scholar
Brozovic, A. et al. Long-term activation of SAPK/JNK, 38 kinase and fas-L expression by cisplatin is attenuated in human carcinoma cells that acquired drug resistance. Int. J. Cancer112, 974–985 (2004). ArticleCASPubMed Google Scholar
Hirsch, D. D. & Stork, P. J. Mitogen-activated protein kinase phosphatases inactivate stress-activated protein kinase pathways in vivo. J. Biol. Chem.272, 4568–4575 (1997). ArticleCASPubMed Google Scholar
Christmann, M., Tomicic, M. T., Aasland, D. & Kaina, B. A role for UV-light-induced c-Fos: stimulation of nucleotide excision repair and protection against sustained JNK activation and apoptosis. Carcinogenesis28, 183–190 (2007). ArticleCASPubMed Google Scholar
Roos, W. P. et al. Intrinsic anticancer drug resistance of malignant melanoma cells is abrogated by IFN-β and valproic acid. Cancer Res.71, 4150–4160 (2011). ArticleCASPubMed Google Scholar
Christmann, M., Verbeek, B., Roos, W. P. & Kaina, B. _O_6-Methylguanine-DNA methyltransferase (MGMT) in normal tissues and tumors: enzyme activity, promoter methylation and immunohistochemistry. Biochim. Biophys. Acta1816, 179–190 (2011). CASPubMed Google Scholar
Weller, M. et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat. Rev. Neurol.6, 39–51 (2010). ArticleCASPubMed Google Scholar
Smith, J. Human Sir2 and the 'silencing' of p53 activity. Trends Cell Biol.12, 404–406 (2002). ArticleCASPubMed Google Scholar
Chen, W. Y. et al. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell123, 437–448 (2005). In this paper, the feedback loop between p53, HIC1 and the deacetylase SIRT1 was described. ArticleCASPubMed Google Scholar
Soengas, M. S. et al. Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature409, 207–211 (2001). ArticleCASPubMed Google Scholar
von Zglinicki, T., Saretzki, G., Ladhoff, J., d' Adda di Fagagna, F. & Jackson, S. P. Human cell senescence as a DNA damage response. Mech. Ageing Dev.126, 111–117 (2005). ArticleCASPubMed Google Scholar
Stevenson, A. F. & Cremer, T. Senescence in vitro and ionising radiations—the human diploid fibroblast model. Mech. Ageing Dev.15, 51–63 (1981). ArticleCASPubMed Google Scholar
Rodier, F. et al. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat. Cell Biol.11, 973–979 (2009). ArticleCASPubMedPubMed Central Google Scholar
Mirzayans, R., Andrais, B., Hansen, G. & Murray, D. Role of p16INK4A in replicative senescence and DNA damage-induced premature senescence in p53-deficient human cells. Biochem. Res. Int.2012, 951574 (2012). ArticlePubMedPubMed CentralCAS Google Scholar
Broccoli, D., Smogorzewska, A., Chong, L. & de Lange, T. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat. Genet.17, 231–235 (1997). ArticleCASPubMed Google Scholar
Fumagalli, M. et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol.14, 355–365 (2012). The authors demonstrated that the shelterin protein TRF2 prevents the completion of DSB repair by NHEJ in telomeres by inhibiting ligase IV, thereby causing persistent ATM-mediated DDR signalling, leading to senescence. ArticleCASPubMedPubMed Central Google Scholar
van Steensel, B., Smogorzewska, A. & de Lange, T. TRF2 protects human telomeres from end-to-end fusions. Cell92, 401–413 (1998). ArticleCASPubMed Google Scholar
Brunori, M. et al. TRF2 inhibition promotes anchorage-independent growth of telomerase-positive human fibroblasts. Oncogene25, 990–997 (2006). ArticleCASPubMed Google Scholar
Hundley, J. E. et al. Increased tumor proliferation and genomic instability without decreased apoptosis in MMTV-ras mice deficient in p53. Mol. Cell. Biol.17, 723–731 (1997). ArticleCASPubMedPubMed Central Google Scholar
Knizhnik, A. V. et al. Survival and death strategies in glioma cells: autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage. PLoS ONE8, e55665 (2013). ArticleCASPubMedPubMed Central Google Scholar
Crighton, D. et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell126, 121–134 (2006). ArticleCASPubMed Google Scholar
Ravikumar, B. et al. Raised intracellular glucose concentrations reduce aggregation and cell death caused by mutant Huntingtin exon 1 by decreasing mTOR phosphorylation and inducing autophagy. Hum. Mol. Genet.12, 985–994 (2003). ArticleCASPubMed Google Scholar
Cao, C. et al. Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells. Cancer Res.66, 10040–10047 (2006). ArticleCASPubMed Google Scholar
Mah, L. Y., O'Prey, J., Baudot, A. D., Hoekstra, A. & Ryan, K. M. DRAM-1 encodes multiple isoforms that regulate autophagy. Autophagy8, 18–28 (2012). ArticleCASPubMed Google Scholar
de Murcia, J. M. et al. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc. Natl Acad. Sci. USA94, 7303–7307 (1997). ArticleCASPubMedPubMed Central Google Scholar
Olson, R. D., Boerth, R. C., Gerber, J. G. & Nies, A. S. Mechanism of adriamycin cardiotoxicity: evidence for oxidative stress. Life Sci.29, 1393–1401 (1981). ArticleCASPubMed Google Scholar
Munoz-Gamez, J. A. et al. PARP-1 is involved in autophagy induced by DNA damage. Autophagy5, 61–74 (2009). ArticleCASPubMed Google Scholar
Rodriguez-Vargas, J. M. et al. ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy. Cell Res.22, 1181–1198 (2012). References 117, 119 and 120 describe the fundamental role of PARP1 for survival and regulation of autophagy following DNA damage. ArticleCASPubMedPubMed Central Google Scholar
Li, L., Ishdorj, G. & Gibson, S. B. Reactive oxygen species regulation of autophagy in cancer: implications for cancer treatment. Free Radic. Biol. Med.53, 1499–1410 (2012). Google Scholar
Lamore, S. D. & Wondrak, G. T. Autophagic-lysosomal dysregulation downstream of cathepsin B inactivation in human skin fibroblasts exposed to UVA. Photochem. Photobiol. Sci.11, 163–172 (2012). ArticleCASPubMed Google Scholar
Suzuki, A. et al. IGF-1 phosphorylates AMPK-α subunit in ATM-dependent and LKB1-independent manner. Biochem. Biophys. Res. Commun.324, 986–992 (2004). ArticleCASPubMed Google Scholar
Ochs, K. & Kaina, B. Apoptosis induced by DNA damage _O_6-methylguanine is Bcl-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res.60, 5815–5824 (2000). CASPubMed Google Scholar
Caporali, S. et al. DNA damage induced by temozolomide signals to both ATM and ATR: role of the mismatch repair system. Mol. Pharmacol.66, 478–491 (2004). CASPubMed Google Scholar
Alexander, A., Kim, J. & Walker, C. L. ATM engages the TSC2/mTORC1 signaling node to regulate autophagy. Autophagy6, 672–673 (2010). ArticlePubMed Google Scholar
Alexander, A. et al. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc. Natl Acad. Sci. USA107, 4153–4158 (2010). This paper describes the link between ATM and mTOR. ArticleCASPubMedPubMed Central Google Scholar
Park, C., Suh, Y. & Cuervo, A. M. Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage. Nat. Commun.6, 6823 (2015). ArticleCASPubMed Google Scholar
Pattingre, S. et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell122, 927–939 (2005). ArticleCASPubMed Google Scholar
Wei, Y., Sinha, S. & Levine, B. Dual role of JNK1-mediated phosphorylation of Bcl-2 in autophagy and apoptosis regulation. Autophagy4, 949–951 (2008). ArticleCASPubMed Google Scholar
Tsujimoto, Y. & Shimizu, S. Another way to die: autophagic programmed cell death. Cell Death Differ.12 (Suppl. 2), 1528–1534 (2005). ArticleCASPubMed Google Scholar
Tsai, W. B., Chung, Y. M., Takahashi, Y., Xu, Z. & Hu, M. C. Functional interaction between FOXO3a and ATM regulates DNA damage response. Nat. Cell Biol.10, 460–467 (2008). ArticleCASPubMedPubMed Central Google Scholar
Kanzawa, T., Kondo, Y., Ito, H., Kondo, S. & Germano, I. Induction of autophagic cell death in malignant glioma cells by arsenic trioxide. Cancer Res.63, 2103–2108 (2003). CASPubMed Google Scholar
Isakson, P., Bjoras, M., Boe, S. O. & Simonsen, A. Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein. Blood116, 2324–2331 (2010). ArticleCASPubMed Google Scholar
Rez, G., Toth, S. & Palfia, Z. Cellular autophagic capacity is highly increased in azaserine-induced premalignant atypical acinar nodule cells. Carcinogenesis20, 1893–1898 (1999). ArticleCASPubMed Google Scholar
Yang, P. M. & Chen, C. C. Life or death? Autophagy in anticancer therapies with statins and histone deacetylase inhibitors. Autophagy7, 107–108 (2011). ArticlePubMed Google Scholar
Gozuacik, D. & Kimchi, A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene23, 2891–2906 (2004). ArticleCASPubMed Google Scholar
Roos, W. P. et al. Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion _O_6-methylguanine. Oncogene26, 186–197 (2007). ArticleCASPubMed Google Scholar
Altieri, D. C. Survivin and IAP proteins in cell-death mechanisms. Biochem. J.430, 199–205 (2010). ArticleCASPubMed Google Scholar
Adida, C. et al. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am. J. Pathol.152, 43–49 (1998). CASPubMedPubMed Central Google Scholar
Santa Cruz Guindalini, R., Mathias Machado, M. C. & Garicochea, B. Monitoring survivin expression in cancer: implications for prognosis and therapy. Mol. Diagn. Ther.17, 331–342 (2013). ArticlePubMedCAS Google Scholar
Greve, B. et al. Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma. Strahlenther. Onkol.188, 1038–1047 (2012). ArticleCASPubMed Google Scholar
Wallace, M. D., Southard, T. L., Schimenti, K. J. & Schimenti, J. C. Role of DNA damage response pathways in preventing carcinogenesis caused by intrinsic replication stress. Oncogene33, 3688–3695 (2014). ArticleCASPubMed Google Scholar
Wu, Y. K. et al. Nuclear survivin expression: a prognostic factor for the response to taxane-platinum chemotherapy in patients with advanced non-small cell lung cancer. Med. Oncol.31, 79 (2014). ArticlePubMedCAS Google Scholar
Sedlak, T. W. et al. Multiple Bcl-2 family members demonstrate selective dimerizations with Bax. Proc. Natl Acad. Sci. USA92, 7834–7838 (1995). ArticleCASPubMedPubMed Central Google Scholar
Boehme, K. A., Kulikov, R. & Blattner, C. p53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK. Proc. Natl Acad. Sci. USA105, 7785–7790 (2008). ArticleCASPubMedPubMed Central Google Scholar
Li, Y., Xiong, H. & Yang, D. Q. Functional switching of ATM: sensor of DNA damage in proliferating cells and mediator of Akt survival signal in post-mitotic human neuron-like cells. Chin. J. Cancer31, 364–372 (2012). ArticlePubMedPubMed CentralCAS Google Scholar
Caporali, S. et al. AKT is activated in an ataxia-telangiectasia and Rad3-related-dependent manner in response to temozolomide and confers protection against drug-induced cell growth inhibition. Mol. Pharmacol.74, 173–183 (2008). ArticleCASPubMed Google Scholar
Fraser, M. et al. MRE11 promotes AKT phosphorylation in direct response to DNA double-strand breaks. Cell Cycle10, 2218–2232 (2011). ArticleCASPubMed Google Scholar
Datta, S. R. et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell91, 231–241 (1997). ArticleCASPubMed Google Scholar
Kim, A. H., Khursigara, G., Sun, X., Franke, T. F. & Chao, M. V. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol. Cell. Biol.21, 893–901 (2001). ArticleCASPubMedPubMed Central Google Scholar
Cardone, M. H. et al. Regulation of cell death protease caspase-9 by phosphorylation. Science282, 1318–1321 (1998). ArticleCASPubMed Google Scholar
Mayo, L. D. & Donner, D. B. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc. Natl Acad. Sci. USA98, 11598–11603 (2001). ArticleCASPubMedPubMed Central Google Scholar
Wirawan, E. et al. Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis.1, e18 (2010). The importance of caspase cleavage of Beclin 1 in the switch between autophagy and apoptosis is demonstrated in this paper. ArticleCASPubMedPubMed Central Google Scholar
Trichonas, G. et al. Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis. Proc. Natl Acad. Sci. USA107, 21695–21700 (2010). ArticleCASPubMedPubMed Central Google Scholar
Osborn, S. L. et al. Fas-associated death domain (FADD) is a negative regulator of T-cell receptor-mediated necroptosis. Proc. Natl Acad. Sci. USA107, 13034–13039 (2010). ArticleCASPubMedPubMed Central Google Scholar
Vanlangenakker, N., Bertrand, M. J., Bogaert, P., Vandenabeele, P. & Vanden Berghe, T. TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. Cell Death Dis.2, e230 (2011). ArticleCASPubMedPubMed Central Google Scholar
Chan, F. K. et al. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J. Biol. Chem.278, 51613–51621 (2003). ArticleCASPubMed Google Scholar
Hu, X., Han, W. & Li, L. Targeting the weak point of cancer by induction of necroptosis. Autophagy3, 490–492 (2007). ArticleCASPubMed Google Scholar
Skulachev, V. P. Bioenergetic aspects of apoptosis, necrosis and mitoptosis. Apoptosis11, 473–485 (2006). ArticleCASPubMed Google Scholar
Los, M. et al. Activation and caspase-mediated inhibition of PARP: a molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol. Biol. Cell13, 978–988 (2002). ArticleCASPubMedPubMed Central Google Scholar
Newton, K. et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science343, 1357–1360 (2014). ArticleCASPubMed Google Scholar
Duprez, L. et al. Intermediate domain of receptor-interacting protein kinase 1 (RIPK1) determines switch between necroptosis and RIPK1 kinase-dependent apoptosis. J. Biol. Chem.287, 14863–14872 (2012). In references 161–163, the role of PARP1 and RIPK3–RIPK1 was demonstrated in the switch between necroptosis and apoptosis. ArticleCASPubMedPubMed Central Google Scholar
Upton, J. W., Kaiser, W. J. & Mocarski, E. S. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe11, 290–297 (2012). ArticleCASPubMedPubMed Central Google Scholar
Kaiser, W. J. & Offermann, M. K. Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J. Immunol.174, 4942–4952 (2005). ArticleCASPubMed Google Scholar
He, M. X. & He, Y. W. A role for c-FLIP(L) in the regulation of apoptosis, autophagy, and necroptosis in T lymphocytes. Cell Death Differ.20, 188–197 (2013). ArticleCASPubMed Google Scholar
McComb, S. et al. cIAP1 and cIAP2 limit macrophage necroptosis by inhibiting Rip1 and Rip3 activation. Cell Death Differ.19, 1791–1801 (2012). ArticleCASPubMedPubMed Central Google Scholar
Cai, Z. et al. Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat. Cell Biol.16, 55–65 (2014). ArticleCASPubMed Google Scholar
Andrabi, S. A., Dawson, T. M. & Dawson, V. L. Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann. NY Acad. Sci.1147, 233–241 (2008). ArticleCASPubMed Google Scholar
Burkle, A. Poly(ADP-ribose). The most elaborate metabolite of NAD+. FEBS J.272, 4576–4589 (2005). ArticlePubMedCAS Google Scholar
Szabo, C. & Dawson, V. L. Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion. Trends Pharmacol. Sci.19, 287–298 (1998). ArticleCASPubMed Google Scholar
Ying, W., Garnier, P. & Swanson, R. A. NAD+ repletion prevents PARP-1-induced glycolytic blockade and cell death in cultured mouse astrocytes. Biochem. Biophys. Res. Commun.308, 809–813 (2003). ArticleCASPubMed Google Scholar
Osato, K. et al. Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation. Cell Death Dis.1, e84 (2010). ArticleCASPubMedPubMed Central Google Scholar
Leist, M., Single, B., Castoldi, A. F., Kuhnle, S. & Nicotera, P. Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J. Exp. Med.185, 1481–1486 (1997). This paper shows for the first time that the ATP level determines the switch between apoptosis and necrosis. ArticleCASPubMedPubMed Central Google Scholar
Huang, C. T., Huang, D. Y., Hu, C. J., Wu, D. & Lin, W. W. Energy adaptive response during parthanatos is enhanced by PD98059 and involves mitochondrial function but not autophagy induction. Biochim. Biophys. Acta1843, 531–543 (2013). ArticleCAS Google Scholar
Kerr, J. F., Wyllie, A. H. & Currie, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer26, 239–257 (1972). These authors described for the first time that apoptosis is an important cell death mechanism. ArticleCASPubMedPubMed Central Google Scholar
Kroemer, G. et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ.16, 3–11 (2009). ArticleCASPubMed Google Scholar
Tang, H. L., Yuen, K. L., Tang, H. M. & Fung, M. C. Reversibility of apoptosis in cancer cells. Br. J. Cancer100, 118–122 (2009). ArticleCASPubMed Google Scholar
Maynard, S. et al. Human embryonic stem cells have enhanced repair of multiple forms of DNA damage. Stem Cells26, 2266–2274 (2008). ArticlePubMedPubMed Central Google Scholar
Bauer, M. et al. Human monocytes are severely impaired in base and DNA double-strand break repair that renders them vulnerable to oxidative stress. Proc. Natl Acad. Sci. USA108, 21105–21110 (2011). ArticleCASPubMedPubMed Central Google Scholar
Narciso, L. et al. Terminally differentiated muscle cells are defective in base excision DNA repair and hypersensitive to oxygen injury. Proc. Natl Acad. Sci. USA104, 17010–17015 (2007). ArticleCASPubMedPubMed Central Google Scholar
Kauffmann, A. et al. High expression of DNA repair pathways is associated with metastasis in melanoma patients. Oncogene27, 565–573 (2008). ArticleCASPubMed Google Scholar
Tomicic, M. T. et al. Translesion polymerase eta is upregulated by cancer therapeutics and confers anticancer drug resistance. Cancer Res.74, 5585–5596 (2014). ArticleCASPubMed Google Scholar
Roos, W. P., Christmann, M., Fraser, S. T. & Kaina, B. Mouse embryonic stem cells are hypersensitive to apoptosis triggered by the DNA damage _O_6-methylguanine due to high E2F1 regulated mismatch repair. Cell Death Differ.14, 1422–1432 (2007). ArticleCASPubMed Google Scholar
Volcic, M. et al. NF-κB regulates DNA double-strand break repair in conjunction with BRCA1-CtIP complexes. Nucleic Acids Res.40, 181–195 (2012). ArticleCASPubMed Google Scholar
Huang, T. T., Wuerzberger-Davis, S. M., Wu, Z. H. & Miyamoto, S. Sequential modification of NEMO/IKKγ by SUMO-1 and ubiquitin mediates NF-κB activation by genotoxic stress. Cell115, 565–576 (2003). ArticleCASPubMed Google Scholar
Cai, Q. & Robertson, E. S. Ubiquitin/SUMO modification regulates VHL protein stability and nucleocytoplasmic localization. PLoS ONE5, e12636 (2010). ArticlePubMedPubMed CentralCAS Google Scholar
Hur, G. M. et al. The death domain kinase RIP has an essential role in DNA damage-induced NF-κB activation. Genes Dev.17, 873–882 (2003). ArticleCASPubMedPubMed Central Google Scholar
Brzoska, K. & Szumiel, I. Signalling loops and linear pathways: NF-κB activation in response to genotoxic stress. Mutagenesis24, 1–8 (2009). ArticleCASPubMed Google Scholar
Lee, H. H., Dadgostar, H., Cheng, Q., Shu, J. & Cheng, G. NF-κB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes. Proc. Natl Acad. Sci. USA96, 9136–9141 (1999). ArticleCASPubMedPubMed Central Google Scholar
Chu, Z. L. et al. Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. Proc. Natl Acad. Sci. USA94, 10057–10062 (1997). ArticleCASPubMedPubMed Central Google Scholar
Wang, C. Y., Mayo, M. W., Korneluk, R. G., Goeddel, D. V. & Baldwin, A. S. Jr. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science281, 1680–1683 (1998). ArticleCASPubMed Google Scholar
Zhou, A., Scoggin, S., Gaynor, R. B. & Williams, N. S. Identification of NF-κB-regulated genes induced by TNFα utilizing expression profiling and RNA interference. Oncogene22, 2054–2064 (2003). ArticleCASPubMed Google Scholar
Cusack, J. C. Jr et al. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-κB inhibition. Cancer Res.61, 3535–3540 (2001). CASPubMed Google Scholar
Yao, R. & Cooper, G. M. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science267, 2003–2006 (1995). ArticleCASPubMed Google Scholar
Wendel, H. G. et al. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature428, 332–337 (2004). ArticleCASPubMed Google Scholar
Toulany, M. et al. Akt promotes post-irradiation survival of human tumor cells through initiation, progression, and termination of DNA-PKcs-dependent DNA double-strand break repair. Mol. Cancer Res.10, 945–957 (2012). ArticleCASPubMed Google Scholar