Sixième réunion du GdR Architecture et Dynamique Nucléaire (ADN)

The cohesin complex is required to maintain chromosome integrity at DSB sites

Non programmé

15m

Orateur

Dr karine dubrana (IRCM-CEA)

Description

A single DSB can be lethal if unrepaired, particularly in a haploid organism like yeast, and may lead to loss of genetic information and chromosome rearrangements if repaired improperly. In this context, maintaining DSB extremities in close proximity until repair is likely a crucial step to avoid illegitimate joining or initiation of independent recombination events from unrelated chromosome loci that would give rise to deleterious translocations. To overcome this dramatic event, the DNA damage response (DDR) implements a protein bridge that holds the two DSB ends together and so preserve its integrity. In S. cerevisiae, at least two pathways have been described. One involves a physical bridging by the MRX, the other requires formation of ssDNA, notably by the Exo1 exonuclease. We show here that the cohesin and SMC5/6 complexes, that share a common 3D structure with MRX and are recruited to DSB, play major roles in maintaining DSB end bridging. Our genetic analysis shows that DSB end tethering requires cohesin loading and that cohesin and SMC5/6 act in the same pathway in part independently of Mre11. We also show that cohesin and SMC5/6 work with Exo1 defining a pathway that act in parallel to MRX. Our data support a model in which cohesin recruitment to DSB mediated both by MRX and by ssDNA formation allows to entrap DSB proximal DNA in a loop that avoid DSB end separation.