Powerful mutators lurking in the genome - PubMed (original) (raw)
Review
Powerful mutators lurking in the genome
Vincent Petit et al. Philos Trans R Soc Lond B Biol Sci. 2009.
Abstract
The human genome encodes numerous enzymes capable of deaminating polynucleotides. While they are capable of exquisite specificity, occasionally they result in hypermutation where up to 90 per cent of cytidine or adenosine residues may be edited. As such, they constitute a formidable anti-viral barrier, for no virus can survive such a high mutation rate. As the APOBEC3 group of cytidine deaminases edit single-stranded viral DNA, the crucial question is can they hyperedit chromosomal DNA? Everything points to a positive answer. Nonetheless, hypermutants per se have not yet been described, probably being countered by highly efficient mismatch repair. For the APOBEC3 genes, not only is their physiological function unknown, but also their role in the induction of cancer remains to be determined. Yet given the pace of research, all this is certain to change in the next few years.
Figures
Figure 1
Selective amplification of AT- and GC-rich DNA. (a) PCR amplification of molecular clones of HIV-1 differing by between 0 and 18 G→A transitions at the non-restrictive and restrictive temperatures of 95 and 83°C, respectively. At 83°C, only clones containing G→A transitions could be amplified. A sample of a HIVΔ_vif_ virus from a molecular clone transfected on to 293T cells and subsequently used to infect PBMCs (peripheral blood mononuclear cells) was also amplified at 83°C. Cloning and sequencing showed the genomes to be G→A hypermutants resulting from APOBEC3G editing of viral cDNA. (b) 3DIPCR amplification of measles virus RNA produced in an interferon type I (i) insensitive (Vero) and (ii) sensitive (MRC5) cell line. (iv) For the MRC5 culture, DNA products could be recovered using a Td as low as 65°C, compared with (iii) the Vero control (67.4°C). Cloning and sequencing showed that the lower temperature products represent measles virus genomes edited by ADAR-1L.
Figure 2
Chemistry of nucleotide deamination. (a) The products of APOBEC and ADAR deamination are uridine and inosine: (i) cytidine deamination C→U and (ii) adenine deamination A→I. (b) To enable PCR-based amplification of GC-rich DNA, two non-natural dNTPs are used. (i) Diaminopurine is an adenosine analogue and base-pairs with thymidine via three hydrogen bonds. (ii) Inosine pairs mainly with cytidine via two hydrogen bonds. Exploration of the PCR denaturation temperature allows selective amplification of GC-rich DNA, which in the form of TCID DNA, as opposed to TCGA DNA, melts at lower temperatures.
Figure 3
AID ‘only’ edited transcribed human Vk1 sequences. (a) A single representative example is given. (b) Statistics of seven sequences bearing GC→AT transitions only. (c) The nucleotide context of the 38 GC→AT transitions resembles closely that of AID, which is WRCW, where W=A,T.
Figure 4
Phylogenic relationships among human APOBEC3 cytidine deamination domains (CDDs). The SplitsTree was made using protein sequences with APOBEC2 (hA2) and AID given as outliers. The CDD domains of the double-domain hA3s have been split and analysed as hA3Bn, hA3Bc, etc. where n and c indicate the N- and C-terminal domains, respectively. Those that edit HPV DNA have been highlighted.
Figure 5
APOBEC3 editing of HPV DNA in vivo. (a) Sample HPV1a.1. A small selection of HPV1a-edited DNA from a planter wart. Only sequence differences are given with respect to the unedited reference sequence. As only a fraction of the sequences are shown, the numbers to the right indicate the total number of mutations per sequence. (b) Dinucleotide context of HPV1a-edited sites where the dot indicates the edited site. The data for A3A, A3C and A3H were derived from transfection experiments. (c) Sample HPV16.29. A small selection of HPV16-edited DNA from a pre-cancerous cervical biopsy. Legend same as figure 5_a_. The TATA box within the promoter region is highlighted. (d) Dinucleotide context of HPV16-edited sites where the dot indicates the edited site. Black bar, experimental; grey bar, in vivo.
Similar articles
- Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism.
Suspène R, Aynaud MM, Guétard D, Henry M, Eckhoff G, Marchio A, Pineau P, Dejean A, Vartanian JP, Wain-Hobson S. Suspène R, et al. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4858-63. doi: 10.1073/pnas.1009687108. Epub 2011 Mar 2. Proc Natl Acad Sci U S A. 2011. PMID: 21368204 Free PMC article. - APOBEC3 proteins and genomic stability: the high cost of a good defense.
Narvaiza I, Landry S, Weitzman MD. Narvaiza I, et al. Cell Cycle. 2012 Jan 1;11(1):33-8. doi: 10.4161/cc.11.1.18706. Epub 2012 Jan 1. Cell Cycle. 2012. PMID: 22157092 Free PMC article. - Extensive editing of both hepatitis B virus DNA strands by APOBEC3 cytidine deaminases in vitro and in vivo.
Suspène R, Guétard D, Henry M, Sommer P, Wain-Hobson S, Vartanian JP. Suspène R, et al. Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8321-6. doi: 10.1073/pnas.0408223102. Epub 2005 May 26. Proc Natl Acad Sci U S A. 2005. PMID: 15919829 Free PMC article. - Retroviral restriction by APOBEC proteins.
Harris RS, Liddament MT. Harris RS, et al. Nat Rev Immunol. 2004 Nov;4(11):868-77. doi: 10.1038/nri1489. Nat Rev Immunol. 2004. PMID: 15516966 Review. - Hepatitis B: modern concepts in pathogenesis--APOBEC3 cytidine deaminases as effectors in innate immunity against the hepatitis B virus.
Bonvin M, Greeve J. Bonvin M, et al. Curr Opin Infect Dis. 2008 Jun;21(3):298-303. doi: 10.1097/QCO.0b013e3282fe1bb2. Curr Opin Infect Dis. 2008. PMID: 18448976 Review.
Cited by
- A-to-I editing of Malacoherpesviridae RNAs supports the antiviral role of ADAR1 in mollusks.
Rosani U, Bai CM, Maso L, Shapiro M, Abbadi M, Domeneghetti S, Wang CM, Cendron L, MacCarthy T, Venier P. Rosani U, et al. BMC Evol Biol. 2019 Jul 23;19(1):149. doi: 10.1186/s12862-019-1472-6. BMC Evol Biol. 2019. PMID: 31337330 Free PMC article. - Impact of DNA lesion repair, replication and formation on the mutational spectra of environmental carcinogens: Aflatoxin B1 as a case study.
Fedeles BI, Essigmann JM. Fedeles BI, et al. DNA Repair (Amst). 2018 Nov;71:12-22. doi: 10.1016/j.dnarep.2018.08.008. Epub 2018 Aug 25. DNA Repair (Amst). 2018. PMID: 30309820 Free PMC article. Review. - APOBEC3A/B deletion polymorphism and cancer risk.
Gansmo LB, Romundstad P, Hveem K, Vatten L, Nik-Zainal S, Lønning PE, Knappskog S. Gansmo LB, et al. Carcinogenesis. 2018 Feb 9;39(2):118-124. doi: 10.1093/carcin/bgx131. Carcinogenesis. 2018. PMID: 29140415 Free PMC article. - Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.
Nik-Zainal S, Wedge DC, Alexandrov LB, Petljak M, Butler AP, Bolli N, Davies HR, Knappskog S, Martin S, Papaemmanuil E, Ramakrishna M, Shlien A, Simonic I, Xue Y, Tyler-Smith C, Campbell PJ, Stratton MR. Nik-Zainal S, et al. Nat Genet. 2014 May;46(5):487-91. doi: 10.1038/ng.2955. Epub 2014 Apr 13. Nat Genet. 2014. PMID: 24728294 Free PMC article. - Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand breaks leading to cell stress and death.
Mussil B, Suspène R, Aynaud MM, Gauvrit A, Vartanian JP, Wain-Hobson S. Mussil B, et al. PLoS One. 2013 Aug 20;8(8):e73641. doi: 10.1371/journal.pone.0073641. eCollection 2013. PLoS One. 2013. PMID: 23977391 Free PMC article.
References
- Abudu A., Takaori-Kondo A., Izumi T., Shirakawa K., Kobayashi M., Sasada A., Fukunaga K., Uchiyama T. Murine retrovirus escapes from murine APOBEC3 via two distinct novel mechanisms. Curr. Biol. 2006;16:1565–1570. doi:10.1016/j.cub.2006.06.055 - DOI - PubMed
- Andersen P.R., Barbacid M., Tronick S.R., Clark H.F., Aaronson S.A. Evolutionary relatedness of viper and primate endogenous retroviruses. Science. 1979;204:318–321. doi:10.1126/science.219480 - DOI - PubMed
- Arbyn M., Dillner J. Review of current knowledge on HPV vaccination: an appendix to the European Guidelines for Quality Assurance in Cervical Cancer Screening. J. Clin. Virol. 2007;38:189–197. doi:10.1016/j.jcv.2006.12.009 - DOI - PubMed
- Armitage A.E., et al. Conserved footprints of APOBEC3G on hypermutated human immunodeficiency virus type 1 and human endogenous retrovirus HERV-K(HML2) sequences. J. Virol. 2008;82:8743–8761. doi:10.1128/JVI.00584-08 - DOI - PMC - PubMed
- Athanasiadis A., Rich A., Maas S. Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biol. 2004;2:e391. doi:10.1371/journal.pbio.0020391 - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials