DNA Damage Response Pathway Uses Histone Modification to Assemble a Double-Strand Break-Specific Cohesin Domain

• Published in: Molecular cell Vol. 16; no. 6; pp. 991 - 1002
• Main Authors: Ünal, Elçin, Arbel-Eden, Ayelet, Sattler, Ulrike, Shroff, Robert, Lichten, Michael, Haber, James E., Koshland, Douglas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.12.2004
• Subjects: Cell Cycle Proteins - metabolism; Checkpoint Kinase 2; Chromosomal Proteins, Non-Histone; Cohesins; DNA - metabolism; DNA Damage - physiology; DNA Repair - physiology; Endodeoxyribonucleases - metabolism; Exodeoxyribonucleases - metabolism; Fungal Proteins; Gene Conversion - physiology; Histones - metabolism; Nuclear Proteins - metabolism; Protein Serine-Threonine Kinases - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2004.11.027

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.