Guardian of Genome Integrity: Cohesin and Dna Damagerepair: Characterization of the Cohesin Complex During Dnadouble-strand Break Response

Chromosome structure is shaped by the proteincomplexes that contain members of the StructuralMaintenance of Chromosome (SMC) family. One of theseprotein complexes called cohesin tethers replicatedchromosomes to mediate sister chromatidcohesion. Sister chromatid cohesion was thought toplay only an indirect role in DNA damage repair. Inthis book, we report our detailed analysis of cohesinin response to a particular type of DNA damage calledDNA double-strand breaks (DSBs). There are three majorconclusions from this work. First, DSBs induce de novorecruitment of cohesins to the broken chromosomes. Second, DSBs induce activation of sister chromatidcohesion by a replication-independent mechanism. Finally, the DSB-induced cohesin is necessary for theefficient repair of DNA breaks. Altogether, ourresults implicate the direct involvement of cohesincomplex in the maintenance of genomic integrity uponDNA breaks and suggest that perturbations ofDSB-specific cohesin pathway could play a role intumorigenesis.