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Molecular Cell, Volume 31, Issue 1, 11 July 2008, Pages 47-56
Jill M. Heidinger-Pauli, Elçin Ünal, Vincent Guacci and Douglas Koshland
SummaryCohesin, the protein complex that mediates sister chromatid cohesion, is required for faithful chromosome segregation and efficient repair of double-strand breaks (DSBs). Cohesion generation is normally restricted to S phase. However, in G2/M, a DSB activates cohesion generation near the DSB and genome-wide. Here, using budding yeast, we show that DSB-induced cohesion occurs when cohesin contains the kleisin subunit, Mcd1 (Scc1), but not when Mcd1 is replaced by its meiotic isoform, Rec8. We exploit this divergence to demonstrate that serine 83 of Mcd1 and the Chk1 kinase are critical determinants for DSB-induced cohesion. We propose that a DSB in G2/M activates Mec1 (ATR), which in turn stimulates Chk1-dependent phosphorylation of Mcd1 at serine 83. Serine 83 phosphorylation promotes chromatin-bound cohesin to become cohesive.
Summary | Full Text | PDF (1022 kb) - On the Road to RepairOn the Road to Repair
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Michael J Matunis
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Summary | Full Text | PDF (70 kb) - PCNA Ubiquitination and REV1 Define Temporally Distinct Mech...PCNA Ubiquitination and REV1 Define Temporally Distinct Mechanisms for Controlling Translesion Synthesis in the Avian Cell Line DT40
Molecular Cell, Volume 30, Issue 4, 23 May 2008, Pages 519-529
Charlotte E. Edmunds, Laura J. Simpson and Julian E. Sale
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Copyright © 2004 Cell Press. All rights reserved.
Molecular Cell, Volume 16, Issue 6, 991-1002, 22 December 2004
doi:10.1016/j.molcel.2004.11.027
Article
DNA Damage Response Pathway Uses Histone Modification to Assemble a Double-Strand Break-Specific Cohesin Domain
Elçin Ünal1, 2, Ayelet Arbel-Eden3, Ulrike Sattler3, Robert Shroff4, Michael Lichten4, James E. Haber3 and Douglas Koshland*, 1, 
1 Howard Hughes Medical Institute, Department of Embryology, The Carnegie Institution of Washington, Baltimore, MD 21210 USA
2 Department of Biology, Johns Hopkins University, Baltimore, MD 21218 USA
3 Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454 USA
4 Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA
Correspondence: Douglas Koshland, (410) 554-1216 (phone), (410) 243-6311 (fax)Summary
The postreplicative repair of double-strand breaks (DSBs) is thought to require sister chromatid cohesion, provided by the cohesin complex along the chromosome arms. A further specialized role for cohesin in DSB repair is suggested by its de novo recruitment to regions of DNA damage in mammals. Here, we show in budding yeast that a single DSB induces the formation of a ∼100 kb cohesin domain around the lesion. Our analyses suggest that the primary DNA damage checkpoint kinases Mec1p and Tel1p phosphorylate histone H2AX to generate a large domain, which is permissive for cohesin binding. Cohesin binding to the phospho-H2AX domain is enabled by Mre11p, a component of a critical repair complex, and Scc2p, a component of the cohesin loading machinery that is necessary for sister chromatid cohesion. We also provide evidence that the DSB-induced cohesin domain functions in postreplicative repair.
