Evidence that the ATR/Chk1 pathway maintains normal replication fork progression during unperturbed S phase - PubMed (original) (raw)
Review
doi: 10.4161/cc.5.19.3256. Epub 2006 Oct 1.
Affiliations
- PMID: 16969104
- DOI: 10.4161/cc.5.19.3256
Review
Evidence that the ATR/Chk1 pathway maintains normal replication fork progression during unperturbed S phase
Eva Petermann et al. Cell Cycle. 2006 Oct.
Abstract
If cells are treated with DNA damaging agents or inhibitors that interfere with ongoing DNA replication, the intra-S and S/M checkpoints delay progression through S phase and mitotic entry, respectively, to allow time for DNA repair and replication restart. In vertebrates, these checkpoint responses to replication blocks are largely mediated by the sensor kinase ATR and its major downstream effector kinase Chk1. Increasing evidence suggests that the ATR pathway is also vital in the absence of exogenous stresses, i.e., during "unperturbed" replication. Both ATR and Chk1 are essential proteins in vertebrates, and lack of components of the ATR/Chk1 pathway can result in impaired replication and spontaneous DNA damage. Here we give an overview of how the ATR/Chk1 pathway responds to exogenously blocked replication and then describe evidence for roles of this pathway during replication in an unperturbed S phase.
Similar articles
- Separation of intra-S checkpoint protein contributions to DNA replication fork protection and genomic stability in normal human fibroblasts.
Smith-Roe SL, Patel SS, Zhou Y, Simpson DA, Rao S, Ibrahim JG, Cordeiro-Stone M, Kaufmann WK. Smith-Roe SL, et al. Cell Cycle. 2013 Jan 15;12(2):332-45. doi: 10.4161/cc.23177. Epub 2012 Jan 15. Cell Cycle. 2013. PMID: 23255133 Free PMC article. - ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage.
Sørensen CS, Syljuåsen RG, Lukas J, Bartek J. Sørensen CS, et al. Cell Cycle. 2004 Jul;3(7):941-5. Epub 2004 Jul 13. Cell Cycle. 2004. PMID: 15190204 - An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage.
Heffernan TP, Simpson DA, Frank AR, Heinloth AN, Paules RS, Cordeiro-Stone M, Kaufmann WK. Heffernan TP, et al. Mol Cell Biol. 2002 Dec;22(24):8552-61. doi: 10.1128/MCB.22.24.8552-8561.2002. Mol Cell Biol. 2002. PMID: 12446774 Free PMC article. - Mechanisms of ATR-mediated checkpoint signalling.
Smits VA, Warmerdam DO, Martin Y, Freire R. Smits VA, et al. Front Biosci (Landmark Ed). 2010 Jun 1;15(3):840-53. doi: 10.2741/3649. Front Biosci (Landmark Ed). 2010. PMID: 20515729 Review. - The ATR pathway: fine-tuning the fork.
Paulsen RD, Cimprich KA. Paulsen RD, et al. DNA Repair (Amst). 2007 Jul 1;6(7):953-66. doi: 10.1016/j.dnarep.2007.02.015. Epub 2007 May 24. DNA Repair (Amst). 2007. PMID: 17531546 Review.
Cited by
- Starting DNA Synthesis: Initiation Processes during the Replication of Chromosomal DNA in Humans.
Nasheuer HP, Meaney AM. Nasheuer HP, et al. Genes (Basel). 2024 Mar 14;15(3):360. doi: 10.3390/genes15030360. Genes (Basel). 2024. PMID: 38540419 Free PMC article. Review. - Analysis of differences in intestinal flora associated with different BMI status in colorectal cancer patients.
Huang Y, Huang X, Wang Z, He F, Huang Z, Chen C, Tang B, Qin M, Wu Y, Long C, Tang W, Mo X, Liu J. Huang Y, et al. J Transl Med. 2024 Feb 9;22(1):142. doi: 10.1186/s12967-024-04903-7. J Transl Med. 2024. PMID: 38331839 Free PMC article. - ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei.
Joo YK, Black EM, Trier I, Haakma W, Zou L, Kabeche L. Joo YK, et al. Mol Cell. 2023 Oct 19;83(20):3642-3658.e4. doi: 10.1016/j.molcel.2023.09.003. Epub 2023 Oct 2. Mol Cell. 2023. PMID: 37788673 Free PMC article. - The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.
Saldanha J, Rageul J, Patel JA, Kim H. Saldanha J, et al. Int J Mol Sci. 2023 Jun 22;24(13):10488. doi: 10.3390/ijms241310488. Int J Mol Sci. 2023. PMID: 37445667 Free PMC article. Review. - A small molecule inhibitor of the UBE2F-CRL5 axis induces apoptosis and radiosensitization in lung cancer.
Xu T, Ma Q, Li Y, Yu Q, Pan P, Zheng Y, Li Z, Xiong X, Hou T, Yu B, Liu H, Sun Y. Xu T, et al. Signal Transduct Target Ther. 2022 Oct 17;7(1):354. doi: 10.1038/s41392-022-01182-w. Signal Transduct Target Ther. 2022. PMID: 36253371 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous