Mre11 Complex Links Sister Chromatids to Promote Repair of a Collapsed Replication Fork

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2018 Aug 15

PMID 30104346

Citations 15

Authors

Min Zhu

Hongchang Zhao

Oliver Limbo

Paul Russell

Affiliations

Soon will be listed here.

Abstract

Collapsed replication forks, which are a major source of DNA double-strand breaks (DSBs), are repaired by sister chromatid recombination (SCR). The Mre11-Rad50-Nbs1 (MRN) protein complex, assisted by CtIP/Sae2/Ctp1, initiates SCR by nucleolytically resecting the single-ended DSB (seDSB) at the collapsed fork. The molecular architecture of the MRN intercomplex, in which zinc hooks at the apices of long Rad50 coiled-coils connect two Mre11-Rad50 complexes, suggests that MRN also structurally assists SCR. Here, Rad50 ChIP assays in show that MRN sequentially localizes with the seDSB and sister chromatid at a collapsed replication fork. Ctp1, which has multivalent DNA-binding and DNA-bridging activities, has the same DNA interaction pattern. Provision of an intrachromosomal repair template alleviates the nonnucleolytic requirement for MRN to repair the broken fork. Mutations of zinc-coordinating cysteines in the Rad50 hook severely impair SCR. These data suggest that the MRN complex facilitates SCR by linking the seDSB and sister chromatid.

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References

Kowalczykowski S . An Overview of the Molecular Mechanisms of Recombinational DNA Repair. Cold Spring Harb Perspect Biol. 2015; 7(11). PMC: 4632670. DOI: 10.1101/cshperspect.a016410. View

Kaykov A, Arcangioli B . A programmed strand-specific and modified nick in S. pombe constitutes a novel type of chromosomal imprint. Curr Biol. 2004; 14(21):1924-8. DOI: 10.1016/j.cub.2004.10.026. View

Lisby M, Barlow J, Burgess R, Rothstein R . Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell. 2004; 118(6):699-713. DOI: 10.1016/j.cell.2004.08.015. View

Sugawara N, Wang X, Haber J . In vivo roles of Rad52, Rad54, and Rad55 proteins in Rad51-mediated recombination. Mol Cell. 2003; 12(1):209-19. DOI: 10.1016/s1097-2765(03)00269-7. View

Andres S, Appel C, Westmoreland J, Williams J, Nguyen Y, Robertson P . Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair. Nat Struct Mol Biol. 2015; 22(2):158-66. PMC: 4318798. DOI: 10.1038/nsmb.2945. View

Yamada-Inagawa T, Klar A, Dalgaard J . Schizosaccharomyces pombe switches mating type by the synthesis-dependent strand-annealing mechanism. Genetics. 2007; 177(1):255-65. PMC: 2013724. DOI: 10.1534/genetics.107.076315. View

Boddy M, Gaillard P, McDonald W, Shanahan P, Yates 3rd J, Russell P . Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell. 2001; 107(4):537-48. DOI: 10.1016/s0092-8674(01)00536-0. View

Stracker T, Petrini J . The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol. 2011; 12(2):90-103. PMC: 3905242. DOI: 10.1038/nrm3047. View

Rogakou E, Boon C, Redon C, Bonner W . Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 1999; 146(5):905-16. PMC: 2169482. DOI: 10.1083/jcb.146.5.905. View

10.

Styrkarsdottir U, Egel R, Nielsen O . The smt-0 mutation which abolishes mating-type switching in fission yeast is a deletion. Curr Genet. 1993; 23(2):184-6. DOI: 10.1007/BF00352020. View

11.

Hopfner K, Craig L, Moncalian G, Zinkel R, Usui T, Owen B . The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. Nature. 2002; 418(6897):562-6. DOI: 10.1038/nature00922. View

12.

Holmes A, Kaykov A, Arcangioli B . Molecular and cellular dissection of mating-type switching steps in Schizosaccharomyces pombe. Mol Cell Biol. 2004; 25(1):303-11. PMC: 538788. DOI: 10.1128/MCB.25.1.303-311.2005. View

13.

Wolner B, Van Komen S, Sung P, Peterson C . Recruitment of the recombinational repair machinery to a DNA double-strand break in yeast. Mol Cell. 2003; 12(1):221-32. DOI: 10.1016/s1097-2765(03)00242-9. View

14.

Schiller C, Seifert F, Linke-Winnebeck C, Hopfner K . Structural studies of DNA end detection and resection in homologous recombination. Cold Spring Harb Perspect Biol. 2014; 6(10):a017962. PMC: 4176011. DOI: 10.1101/cshperspect.a017962. View

15.

Williams R, Moncalian G, Williams J, Yamada Y, Limbo O, Shin D . Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell. 2008; 135(1):97-109. PMC: 2681233. DOI: 10.1016/j.cell.2008.08.017. View

16.

Hohl M, Kochanczyk T, Tous C, Aguilera A, Krezel A, Petrini J . Interdependence of the rad50 hook and globular domain functions. Mol Cell. 2015; 57(3):479-91. PMC: 4527088. DOI: 10.1016/j.molcel.2014.12.018. View

17.

Klar A, Miglio L . Initiation of meiotic recombination by double-strand DNA breaks in S. pombe. Cell. 1986; 46(5):725-31. DOI: 10.1016/0092-8674(86)90348-x. View

18.

Andres S, Williams R . CtIP/Ctp1/Sae2, molecular form fit for function. DNA Repair (Amst). 2017; 56:109-117. PMC: 5543718. DOI: 10.1016/j.dnarep.2017.06.013. View

19.

Akamatsu Y, Dziadkowiec D, Ikeguchi M, Shinagawa H, Iwasaki H . Two different Swi5-containing protein complexes are involved in mating-type switching and recombination repair in fission yeast. Proc Natl Acad Sci U S A. 2003; 100(26):15770-5. PMC: 307643. DOI: 10.1073/pnas.2632890100. View

20.

Nakamura T, Du L, Redon C, Russell P . Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast. Mol Cell Biol. 2004; 24(14):6215-30. PMC: 434244. DOI: 10.1128/MCB.24.14.6215-6230.2004. View