Break-induced Replication Requires All Essential DNA Replication Factors Except Those Specific for Pre-RC Assembly

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2010 Jun 3

PMID 20516198

Citations 111

Authors

John R Lydeard

Zachary Lipkin-Moore

Yi-Jun Sheu

Bruce Stillman

Peter M Burgers

James E Haber

Affiliations

Soon will be listed here.

Abstract

Break-induced replication (BIR) is an efficient homologous recombination (HR) pathway employed to repair a DNA double-strand break (DSB) when homology is restricted to one end. All three major replicative DNA polymerases are required for BIR, including the otherwise nonessential Pol32 subunit. Here we show that BIR requires the replicative DNA helicase (Cdc45, the GINS, and Mcm2-7 proteins) as well as Cdt1. In contrast, both subunits of origin recognition complex (ORC) and Cdc6, which are required to create a prereplication complex (pre-RC), are dispensable. The Cdc7 kinase, required for both initiation of DNA replication and post-replication repair (PRR), is also required for BIR. Ubiquitination and sumoylation of the DNA processivity clamp PCNA play modest roles; in contrast, PCNA alleles that suppress pol32Delta's cold sensitivity fail to suppress its role in BIR, and are by themselves dominant inhibitors of BIR. These results suggest that origin-independent BIR involves cross-talk between normal DNA replication factors and PRR.

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References

Tercero J, Labib K, Diffley J . DNA synthesis at individual replication forks requires the essential initiation factor Cdc45p. EMBO J. 2000; 19(9):2082-93. PMC: 305696. DOI: 10.1093/emboj/19.9.2082. View

Symington L . Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair. Microbiol Mol Biol Rev. 2002; 66(4):630-70, table of contents. PMC: 134659. DOI: 10.1128/MMBR.66.4.630-670.2002. View

Semple J, Da-Silva L, Jervis E, Ah-Kee J, Al-Attar H, Kummer L . An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes. EMBO J. 2006; 25(21):5150-8. PMC: 1630405. DOI: 10.1038/sj.emboj.7601391. View

Kamimura Y, Masumoto H, Sugino A, Araki H . Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication. Mol Cell Biol. 1998; 18(10):6102-9. PMC: 109196. DOI: 10.1128/MCB.18.10.6102. View

Bousset K, Diffley J . The Cdc7 protein kinase is required for origin firing during S phase. Genes Dev. 1998; 12(4):480-90. PMC: 316531. DOI: 10.1101/gad.12.4.480. View

Eissenberg J, Ayyagari R, Gomes X, Burgers P . Mutations in yeast proliferating cell nuclear antigen define distinct sites for interaction with DNA polymerase delta and DNA polymerase epsilon. Mol Cell Biol. 1997; 17(11):6367-78. PMC: 232488. DOI: 10.1128/MCB.17.11.6367. View

Pacek M, Tutter A, Kubota Y, Takisawa H, Walter J . Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication. Mol Cell. 2006; 21(4):581-7. DOI: 10.1016/j.molcel.2006.01.030. View

Sheu Y, Stillman B . The Dbf4-Cdc7 kinase promotes S phase by alleviating an inhibitory activity in Mcm4. Nature. 2010; 463(7277):113-7. PMC: 2805463. DOI: 10.1038/nature08647. View

Zegerman P, Diffley J . Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature. 2006; 445(7125):281-5. DOI: 10.1038/nature05432. View

10.

Haber J . DNA recombination: the replication connection. Trends Biochem Sci. 1999; 24(7):271-5. DOI: 10.1016/s0968-0004(99)01413-9. View

11.

Zhu W, Ukomadu C, Jha S, Senga T, Dhar S, Wohlschlegel J . Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes Dev. 2007; 21(18):2288-99. PMC: 1973143. DOI: 10.1101/gad.1585607. View

12.

Park S, Asano M . The origin recognition complex is dispensable for endoreplication in Drosophila. Proc Natl Acad Sci U S A. 2008; 105(34):12343-8. PMC: 2527913. DOI: 10.1073/pnas.0805189105. View

13.

Gambus A, Jones R, Sanchez-Diaz A, Kanemaki M, van Deursen F, Edmondson R . GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat Cell Biol. 2006; 8(4):358-66. DOI: 10.1038/ncb1382. View

14.

Kamimura Y, Tak Y, Sugino A, Araki H . Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae. EMBO J. 2001; 20(8):2097-107. PMC: 125422. DOI: 10.1093/emboj/20.8.2097. View

15.

Randell J, Bowers J, Rodriguez H, Bell S . Sequential ATP hydrolysis by Cdc6 and ORC directs loading of the Mcm2-7 helicase. Mol Cell. 2006; 21(1):29-39. DOI: 10.1016/j.molcel.2005.11.023. View

16.

Llorente B, Smith C, Symington L . Break-induced replication: what is it and what is it for?. Cell Cycle. 2008; 7(7):859-64. DOI: 10.4161/cc.7.7.5613. View

17.

Wohlschlegel J, Dhar S, Prokhorova T, Dutta A, Walter J . Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45. Mol Cell. 2002; 9(2):233-40. DOI: 10.1016/s1097-2765(02)00456-2. View

18.

Vaze M, Pellicioli A, Lee S, Ira G, Liberi G, Arbel-Eden A . Recovery from checkpoint-mediated arrest after repair of a double-strand break requires Srs2 helicase. Mol Cell. 2002; 10(2):373-85. DOI: 10.1016/s1097-2765(02)00593-2. View

19.

Ricke R, Bielinsky A . Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha. Mol Cell. 2004; 16(2):173-85. DOI: 10.1016/j.molcel.2004.09.017. View

20.

Michel B . Replication fork arrest and DNA recombination. Trends Biochem Sci. 2000; 25(4):173-8. DOI: 10.1016/s0968-0004(00)01560-7. View