Journal of Biological Chemistry
Volume 277, Issue 47, 22 November 2002, Pages 45149-45153
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DNA: REPLICATION REPAIR AND RECOMBINATION
Specific Recruitment of Human Cohesin to Laser-induced DNA Damage*

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Cohesin is a conserved multiprotein complex that plays an essential role in sister chromatid cohesion. During interphase, cohesin is required for the establishment of cohesion following DNA replication. Because cohesin mutants resulted in increased sensitivity to DNA damage, a role for cohesin in DNA repair was also suggested. However, it was unclear whether this was due to general perturbation of cohesion or whether cohesin has a specialized role at the damage site. We therefore used a laser microbeam to create DNA damage at discrete sites in the cell nucleus and observed specificin vivo assembly of proteins at these sites by immunofluorescent detection. We observed that human cohesin is recruited to the damage site immediately after damage induction. Analysis of mutant cells revealed that cohesin recruitment to the damage site is dependent on the DNA double-strand break repair factor Mre11/Rad50 but not ATM or Nbs1. Consistently, Mre11/Rad50 and cohesin interact with each other in an interphase-specific manner. This interaction peaks in S/G2 phase, during which cohesin is recruited to the DNA damage. Our results demonstrate the S/G2-specific and Mre11/Rad50-dependent recruitment of human cohesin to DNA damage, suggesting a specialized subfunction for cohesin in cell cycle-specific DNA double strand break repair.

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This work was supported by a seed grant from the Avon Foundation (to K. Y.), Grant GM59150 from the National Institutes of Health (to K. Y.), the Laser Microbeam and Medical Program (LAMMP) National Institutes of Health Grant RR01192, the Chao Family Cancer Center Optical Biology Shared Resource (CA-62203), and BLI programmatic support from the Department of Energy (DE-FG03-91ER61227).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.