Replication-Coupled DNA Repair

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Jun 8

PMID 31173722

Citations 132

Authors

David Cortez

Affiliations

Soon will be listed here.

Abstract

The replisome quickly and accurately copies billions of DNA bases each cell division cycle. However, it can make errors, especially when the template DNA is damaged. In these cases, replication-coupled repair mechanisms remove the mistake or repair the template lesions to ensure high fidelity and complete copying of the genome. Failures in these genome maintenance activities generate mutations, rearrangements, and chromosome segregation problems that cause many human diseases. In this review, I provide a broad overview of replication-coupled repair pathways, explaining how they fix polymerase mistakes, respond to template damage that acts as obstacles to the replisome, deal with broken forks, and impact human health and disease.

Citing Articles

MUSICiAn: Genome-wide Identification of Genes Involved in DNA Repair via Control-Free Mutational Spectra Analysis.

Seale C, Barazas M, van Schendel R, Tijsterman M, Goncalves J bioRxiv. 2025; .

PMID: 39975194 PMC: 11838396. DOI: 10.1101/2025.01.27.635038.

A tale of two strands: Decoding chromatin replication through strand-specific sequencing.

Li Z, Zhang Z Mol Cell. 2025; 85(2):238-261.

PMID: 39824166 PMC: 11750172. DOI: 10.1016/j.molcel.2024.10.035.

HROB Is Implicated in DNA Replication.

Kutz J, Schmietendorf H, Rahman S, Opel F, Pospiech H Genes (Basel). 2025; 15(12.

PMID: 39766854 PMC: 11675949. DOI: 10.3390/genes15121587.

TTF2 promotes replisome eviction from stalled forks in mitosis.

Can G, Shyian M, Krishnamoorthy A, Lim Y, Wu R, Zaher M bioRxiv. 2024; .

PMID: 39651145 PMC: 11623681. DOI: 10.1101/2024.11.30.626186.

Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities.

Takemon Y, Pleasance E, Gagliardi A, Hughes C, Csizmok V, Wee K Genome Med. 2024; 16(1):136.

PMID: 39578878 PMC: 11583415. DOI: 10.1186/s13073-024-01401-9.

References

Sotiriou S, Kamileri I, Lugli N, Evangelou K, Da-Re C, Huber F . Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks. Mol Cell. 2016; 64(6):1127-1134. PMC: 5179496. DOI: 10.1016/j.molcel.2016.10.038. View

Yuan J, Ghosal G, Chen J . The annealing helicase HARP protects stalled replication forks. Genes Dev. 2009; 23(20):2394-9. PMC: 2764499. DOI: 10.1101/gad.1836409. View

Bubeck D, Reijns M, Graham S, Astell K, Jones E, Jackson A . PCNA directs type 2 RNase H activity on DNA replication and repair substrates. Nucleic Acids Res. 2011; 39(9):3652-66. PMC: 3089482. DOI: 10.1093/nar/gkq980. View

Vujanovic M, Krietsch J, Raso M, Terraneo N, Zellweger R, Schmid J . Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity. Mol Cell. 2017; 67(5):882-890.e5. PMC: 5594246. DOI: 10.1016/j.molcel.2017.08.010. View

Amunugama R, Willcox S, Wu R, Abdullah U, El-Sagheer A, Brown T . Replication Fork Reversal during DNA Interstrand Crosslink Repair Requires CMG Unloading. Cell Rep. 2018; 23(12):3419-3428. PMC: 6086610. DOI: 10.1016/j.celrep.2018.05.061. View

Poole L, Zhao R, Glick G, Lovejoy C, Eischen C, Cortez D . SMARCAL1 maintains telomere integrity during DNA replication. Proc Natl Acad Sci U S A. 2015; 112(48):14864-9. PMC: 4672769. DOI: 10.1073/pnas.1510750112. View

Kleczkowska H, Marra G, Lettieri T, Jiricny J . hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci. Genes Dev. 2001; 15(6):724-36. PMC: 312660. DOI: 10.1101/gad.191201. View

Mijic S, Zellweger R, Chappidi N, Berti M, Jacobs K, Mutreja K . Replication fork reversal triggers fork degradation in BRCA2-defective cells. Nat Commun. 2017; 8(1):859. PMC: 5643541. DOI: 10.1038/s41467-017-01164-5. View

Ceccaldi R, Sarangi P, DAndrea A . The Fanconi anaemia pathway: new players and new functions. Nat Rev Mol Cell Biol. 2016; 17(6):337-49. DOI: 10.1038/nrm.2016.48. View

10.

Poole L, Cortez D . Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability. Crit Rev Biochem Mol Biol. 2017; 52(6):696-714. PMC: 5962345. DOI: 10.1080/10409238.2017.1380597. View

11.

Betous R, Couch F, Mason A, Eichman B, Manosas M, Cortez D . Substrate-selective repair and restart of replication forks by DNA translocases. Cell Rep. 2013; 3(6):1958-69. PMC: 3700663. DOI: 10.1016/j.celrep.2013.05.002. View

12.

Ciccia A, Nimonkar A, Hu Y, Hajdu I, Achar Y, Izhar L . Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. Mol Cell. 2012; 47(3):396-409. PMC: 3613862. DOI: 10.1016/j.molcel.2012.05.024. View

13.

Li H, Cuevas I, Zhang M, Lu C, Alam M, Fu Y . Polymerase-mediated ultramutagenesis in mice produces diverse cancers with high mutational load. J Clin Invest. 2018; 128(9):4179-4191. PMC: 6118636. DOI: 10.1172/JCI122095. View

14.

Semlow D, Zhang J, Budzowska M, Drohat A, Walter J . Replication-Dependent Unhooking of DNA Interstrand Cross-Links by the NEIL3 Glycosylase. Cell. 2016; 167(2):498-511.e14. PMC: 5237264. DOI: 10.1016/j.cell.2016.09.008. View

15.

Ciccia A, Bredemeyer A, Sowa M, Terret M, Jallepalli P, Harper J . The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart. Genes Dev. 2009; 23(20):2415-25. PMC: 2764500. DOI: 10.1101/gad.1832309. View

16.

Larsen N, Gao A, Sparks J, Gallina I, Wu R, Mann M . Replication-Coupled DNA-Protein Crosslink Repair by SPRTN and the Proteasome in Xenopus Egg Extracts. Mol Cell. 2019; 73(3):574-588.e7. PMC: 6375733. DOI: 10.1016/j.molcel.2018.11.024. View

17.

Diplas B, He X, Brosnan-Cashman J, Liu H, Chen L, Wang Z . The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma. Nat Commun. 2018; 9(1):2087. PMC: 5970234. DOI: 10.1038/s41467-018-04448-6. View

18.

Badu-Nkansah A, Mason A, Eichman B, Cortez D . Identification of a Substrate Recognition Domain in the Replication Stress Response Protein Zinc Finger Ran-binding Domain-containing Protein 3 (ZRANB3). J Biol Chem. 2016; 291(15):8251-7. PMC: 5414104. DOI: 10.1074/jbc.M115.709733. View

19.

Mayle R, Campbell I, Beck C, Yu Y, Wilson M, Shaw C . DNA REPAIR. Mus81 and converging forks limit the mutagenicity of replication fork breakage. Science. 2015; 349(6249):742-7. PMC: 4782627. DOI: 10.1126/science.aaa8391. View

20.

Bass T, Luzwick J, Kavanaugh G, Carroll C, Dungrawala H, Glick G . ETAA1 acts at stalled replication forks to maintain genome integrity. Nat Cell Biol. 2016; 18(11):1185-1195. PMC: 5245861. DOI: 10.1038/ncb3415. View