The Regulation of Homologous Recombination by Helicases

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2020 May 7

PMID 32369918

Citations 20

Authors

Eric Huselid

Samuel F Bunting

Affiliations

Soon will be listed here.

Abstract

Homologous recombination is essential for DNA repair, replication and the exchange of genetic material between parental chromosomes during meiosis. The stages of recombination involve complex reorganization of DNA structures, and the successful completion of these steps is dependent on the activities of multiple helicase enzymes. Helicases of many different families coordinate the processing of broken DNA ends, and the subsequent formation and disassembly of the recombination intermediates that are necessary for template-based DNA repair. Loss of recombination-associated helicase activities can therefore lead to genomic instability, cell death and increased risk of tumor formation. The efficiency of recombination is also influenced by the 'anti-recombinase' effect of certain helicases, which can direct DNA breaks toward repair by other pathways. Other helicases regulate the crossover versus non-crossover outcomes of repair. The use of recombination is increased when replication forks and the transcription machinery collide, or encounter lesions in the DNA template. Successful completion of recombination in these situations is also regulated by helicases, allowing normal cell growth, and the maintenance of genomic integrity.

Citing Articles

The human HELQ helicase and XRN2 exoribonuclease cooperate in R-loop resolution.

Pan J, Betts H, Cubbon A, He L, Bolt E, Soultanas P Open Biol. 2025; 15(2):240112.

PMID: 39965657 PMC: 11835494. DOI: 10.1098/rsob.240112.

Research progress on the fanconi anemia signaling pathway in non-obstructive azoospermia.

Xu H, Zhang Y, Wang C, Fu Z, Lv J, Yang Y Front Endocrinol (Lausanne). 2024; 15:1393111.

PMID: 38846492 PMC: 11153779. DOI: 10.3389/fendo.2024.1393111.

Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review).

Lin Y, Jin X Exp Ther Med. 2023; 27(1):33.

PMID: 38125344 PMC: 10731405. DOI: 10.3892/etm.2023.12321.

F-box DNA Helicase 1 (FBH1) Contributes to the Destabilization of DNA Damage Repair Machinery in Human Cancers.

Watson A, Shaffer M, Bouley R, Petreaca R Cancers (Basel). 2023; 15(18).

PMID: 37760409 PMC: 10526855. DOI: 10.3390/cancers15184439.

Archaeal Hel308 suppresses recombination through a catalytic switch that controls DNA annealing.

Lever R, Simmons E, Gamble-Milner R, Buckley R, Harrison C, Parkes A Nucleic Acids Res. 2023; 51(16):8563-8574.

PMID: 37409572 PMC: 10484726. DOI: 10.1093/nar/gkad572.

References

van Brabant A, Ye T, Sanz M, German III J, Ellis N, Holloman W . Binding and melting of D-loops by the Bloom syndrome helicase. Biochemistry. 2000; 39(47):14617-25. DOI: 10.1021/bi0018640. View

Wang A, Kim T, Wagner J, Conti B, Lach F, Huang A . A Dominant Mutation in Human RAD51 Reveals Its Function in DNA Interstrand Crosslink Repair Independent of Homologous Recombination. Mol Cell. 2015; 59(3):478-90. PMC: 4529964. DOI: 10.1016/j.molcel.2015.07.009. View

Tkac J, Xu G, Adhikary H, Young J, Gallo D, Escribano-Diaz C . HELB Is a Feedback Inhibitor of DNA End Resection. Mol Cell. 2016; 61(3):405-418. DOI: 10.1016/j.molcel.2015.12.013. View

Chaganti R, Schonberg S, German J . A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes. Proc Natl Acad Sci U S A. 1974; 71(11):4508-12. PMC: 433916. DOI: 10.1073/pnas.71.11.4508. View

Lee K, Im J, Shibata E, Park J, Handa N, Kowalczykowski S . MCM8-9 complex promotes resection of double-strand break ends by MRE11-RAD50-NBS1 complex. Nat Commun. 2015; 6:7744. PMC: 4525285. DOI: 10.1038/ncomms8744. View

Ward J, Muzzini D, Petalcorin M, Martinez-Perez E, Martin J, Plevani P . Overlapping mechanisms promote postsynaptic RAD-51 filament disassembly during meiotic double-strand break repair. Mol Cell. 2010; 37(2):259-72. DOI: 10.1016/j.molcel.2009.12.026. View

Dyer M, Qadeer Z, Valle-Garcia D, Bernstein E . ATRX and DAXX: Mechanisms and Mutations. Cold Spring Harb Perspect Med. 2017; 7(3). PMC: 5334245. DOI: 10.1101/cshperspect.a026567. View

Costelloe T, Louge R, Tomimatsu N, Mukherjee B, Martini E, Khadaroo B . The yeast Fun30 and human SMARCAD1 chromatin remodellers promote DNA end resection. Nature. 2012; 489(7417):581-4. PMC: 3493121. DOI: 10.1038/nature11353. View

Bugreev D, Yu X, Egelman E, Mazin A . Novel pro- and anti-recombination activities of the Bloom's syndrome helicase. Genes Dev. 2007; 21(23):3085-94. PMC: 2081975. DOI: 10.1101/gad.1609007. View

10.

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

11.

Raynard S, Bussen W, Sung P . A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. J Biol Chem. 2006; 281(20):13861-4. DOI: 10.1074/jbc.C600051200. 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.

Chen H, Lisby M, Symington L . RPA coordinates DNA end resection and prevents formation of DNA hairpins. Mol Cell. 2013; 50(4):589-600. PMC: 3855855. DOI: 10.1016/j.molcel.2013.04.032. View

14.

Zheng X, Prakash R, Saro D, Longerich S, Niu H, Sung P . Processing of DNA structures via DNA unwinding and branch migration by the S. cerevisiae Mph1 protein. DNA Repair (Amst). 2011; 10(10):1034-43. PMC: 3185188. DOI: 10.1016/j.dnarep.2011.08.002. View

15.

Orren D, Theodore S, Machwe A . The Werner syndrome helicase/exonuclease (WRN) disrupts and degrades D-loops in vitro. Biochemistry. 2002; 41(46):13483-8. DOI: 10.1021/bi0266986. View

16.

Datta A, Brosh Jr R . New Insights Into DNA Helicases as Druggable Targets for Cancer Therapy. Front Mol Biosci. 2018; 5:59. PMC: 6028597. DOI: 10.3389/fmolb.2018.00059. View

17.

Patel D, Misenko S, Her J, Bunting S . BLM helicase regulates DNA repair by counteracting RAD51 loading at DNA double-strand break sites. J Cell Biol. 2017; 216(11):3521-3534. PMC: 5674892. DOI: 10.1083/jcb.201703144. View

18.

Aggarwal M, Sommers J, Morris C, Brosh Jr R . Delineation of WRN helicase function with EXO1 in the replicational stress response. DNA Repair (Amst). 2010; 9(7):765-76. PMC: 2893289. DOI: 10.1016/j.dnarep.2010.03.014. View

19.

Bugreev D, Brosh Jr R, Mazin A . RECQ1 possesses DNA branch migration activity. J Biol Chem. 2008; 283(29):20231-42. PMC: 2459305. DOI: 10.1074/jbc.M801582200. View

20.

Shamima Keka I, Mohiuddin , Maede Y, Rahman M, Sakuma T, Honma M . Smarcal1 promotes double-strand-break repair by nonhomologous end-joining. Nucleic Acids Res. 2015; 43(13):6359-72. PMC: 4513880. DOI: 10.1093/nar/gkv621. View