Abstract
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 approximately 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Cycle Proteins / metabolism
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Checkpoint Kinase 2
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Chromosomal Proteins, Non-Histone
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Cohesins
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DNA / metabolism*
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DNA Damage / physiology
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DNA Repair / physiology*
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Endodeoxyribonucleases / metabolism
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Exodeoxyribonucleases / metabolism
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Fungal Proteins
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Gene Conversion / physiology
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Histones / metabolism*
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Nuclear Proteins / metabolism*
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Protein Serine-Threonine Kinases / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / metabolism
Substances
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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Fungal Proteins
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Histones
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Nuclear Proteins
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SCC2 protein, S cerevisiae
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SCC4 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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gamma-H2AX protein, mouse
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DNA
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Checkpoint Kinase 2
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Protein Serine-Threonine Kinases
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RAD53 protein, S cerevisiae
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Endodeoxyribonucleases
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Exodeoxyribonucleases
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MRE11 protein, S cerevisiae