The Helicase Pif1 Functions in the Template Switching Pathway of DNA Damage Bypass

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2018 Aug 15

PMID 30107417

Citations 18

Authors

Nestor Garcia-Rodriguez

Ronald P Wong

Helle D Ulrich

Affiliations

Soon will be listed here.

Abstract

Replication of damaged DNA is challenging because lesions in the replication template frequently interfere with an orderly progression of the replisome. In this situation, complete duplication of the genome is ensured by the action of DNA damage bypass pathways effecting either translesion synthesis by specialized, damage-tolerant DNA polymerases or a recombination-like mechanism called template switching (TS). Here we report that budding yeast Pif1, a helicase known to be involved in the resolution of complex DNA structures as well as the maturation of Okazaki fragments during replication, contributes to DNA damage bypass. We show that Pif1 expands regions of single-stranded DNA, so-called daughter-strand gaps, left behind the replication fork as a consequence of replisome re-priming. This function requires interaction with the replication clamp, proliferating cell nuclear antigen, facilitating its recruitment to damage sites, and complements the activity of an exonuclease, Exo1, in the processing of post-replicative daughter-strand gaps in preparation for TS. Our results thus reveal a novel function of a conserved DNA helicase that is known as a key player in genome maintenance.

Citing Articles

EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells.

Garcia-Rodriguez N, Dominguez-Garcia I, Dominguez-Perez M, Huertas P Nucleic Acids Res. 2024; 52(11):6376-6391.

PMID: 38721777 PMC: 11194085. DOI: 10.1093/nar/gkae317.

Avidity-based biosensors for ubiquitylated PCNA reveal choreography of DNA damage bypass.

Yakoub G, Choi Y, Wong R, Strauch T, Ann K, Cohen R Sci Adv. 2023; 9(36):eadf3041.

PMID: 37672592 PMC: 10482348. DOI: 10.1126/sciadv.adf3041.

Integration of DNA Repair, Antigenic Variation, Cytoadhesion, and Chance in Survival: A Perspective.

Allred D Front Cell Infect Microbiol. 2022; 12:869696.

PMID: 35493746 PMC: 9047050. DOI: 10.3389/fcimb.2022.869696.

Mechanistic Insight Into Cadmium- and Zinc-Induced Inactivation of the Pif1 Helicase.

Zhang B, Zhang Q, Zhu X, Li D, Duan X, Jin J Front Mol Biosci. 2022; 8:778647.

PMID: 35127815 PMC: 8815974. DOI: 10.3389/fmolb.2021.778647.

Non-Recombinogenic Functions of Rad51, BRCA2, and Rad52 in DNA Damage Tolerance.

Prado F Genes (Basel). 2021; 12(10).

PMID: 34680945 PMC: 8535942. DOI: 10.3390/genes12101550.

References

Davies A, Huttner D, Daigaku Y, Chen S, Ulrich H . Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a. Mol Cell. 2008; 29(5):625-36. PMC: 2507760. DOI: 10.1016/j.molcel.2007.12.016. View

Lahaye A, Leterme S, Foury F . PIF1 DNA helicase from Saccharomyces cerevisiae. Biochemical characterization of the enzyme. J Biol Chem. 1993; 268(35):26155-61. View

Lundin C, North M, Erixon K, Walters K, Jenssen D, Goldman A . Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks. Nucleic Acids Res. 2005; 33(12):3799-811. PMC: 1174933. DOI: 10.1093/nar/gki681. View

Bae S, Seo Y . Characterization of the enzymatic properties of the yeast dna2 Helicase/endonuclease suggests a new model for Okazaki fragment processing. J Biol Chem. 2000; 275(48):38022-31. DOI: 10.1074/jbc.M006513200. View

Schulz V, Zakian V . The saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation. Cell. 1994; 76(1):145-55. DOI: 10.1016/0092-8674(94)90179-1. View

Wei X, Zhang B, Bazeille N, Yu Y, Liu N, Rene B . A 3'-5' exonuclease activity embedded in the helicase core domain of Candida albicans Pif1 helicase. Sci Rep. 2017; 7:42865. PMC: 5316945. DOI: 10.1038/srep42865. View

Ball L, Zhang K, Cobb J, Boone C, Xiao W . The yeast Shu complex couples error-free post-replication repair to homologous recombination. Mol Microbiol. 2009; 73(1):89-102. DOI: 10.1111/j.1365-2958.2009.06748.x. View

Vanoli F, Fumasoni M, Szakal B, Maloisel L, Branzei D . Replication and recombination factors contributing to recombination-dependent bypass of DNA lesions by template switch. PLoS Genet. 2010; 6(11):e1001205. PMC: 2978687. DOI: 10.1371/journal.pgen.1001205. View

Karras G, Jentsch S . The RAD6 DNA damage tolerance pathway operates uncoupled from the replication fork and is functional beyond S phase. Cell. 2010; 141(2):255-67. DOI: 10.1016/j.cell.2010.02.028. View

10.

Liberi G, Maffioletti G, Lucca C, Chiolo I, Baryshnikova A, Cotta-Ramusino C . Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase. Genes Dev. 2005; 19(3):339-50. PMC: 546512. DOI: 10.1101/gad.322605. View

11.

Dewar J, Lydall D . Pif1- and Exo1-dependent nucleases coordinate checkpoint activation following telomere uncapping. EMBO J. 2010; 29(23):4020-34. PMC: 3020640. DOI: 10.1038/emboj.2010.267. View

12.

Moldovan G, Pfander B, Jentsch S . PCNA, the maestro of the replication fork. Cell. 2007; 129(4):665-79. DOI: 10.1016/j.cell.2007.05.003. View

13.

Branzei D, Vanoli F, Foiani M . SUMOylation regulates Rad18-mediated template switch. Nature. 2008; 456(7224):915-20. DOI: 10.1038/nature07587. View

14.

Choi K, Batke S, Szakal B, Lowther J, Hao F, Sarangi P . Concerted and differential actions of two enzymatic domains underlie Rad5 contributions to DNA damage tolerance. Nucleic Acids Res. 2015; 43(5):2666-77. PMC: 4357696. DOI: 10.1093/nar/gkv004. View

15.

Chisholm K, Aubert S, Freese K, Zakian V, King M, Welcsh P . A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1. PLoS One. 2012; 7(2):e30748. PMC: 3276492. DOI: 10.1371/journal.pone.0030748. View

16.

Yuan J, Ghosal G, Chen J . The HARP-like domain-containing protein AH2/ZRANB3 binds to PCNA and participates in cellular response to replication stress. Mol Cell. 2012; 47(3):410-21. PMC: 3601832. DOI: 10.1016/j.molcel.2012.05.025. View

17.

Ellison V, Stillman B . Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA. PLoS Biol. 2003; 1(2):E33. PMC: 261875. DOI: 10.1371/journal.pbio.0000033. View

18.

Boule J, Zakian V . Roles of Pif1-like helicases in the maintenance of genomic stability. Nucleic Acids Res. 2006; 34(15):4147-53. PMC: 1616966. DOI: 10.1093/nar/gkl561. View

19.

Friedberg E . Suffering in silence: the tolerance of DNA damage. Nat Rev Mol Cell Biol. 2005; 6(12):943-53. DOI: 10.1038/nrm1781. View

20.

Masuda-Sasa T, Imamura O, Campbell J . Biochemical analysis of human Dna2. Nucleic Acids Res. 2006; 34(6):1865-75. PMC: 1428797. DOI: 10.1093/nar/gkl070. View