hide
Free keywords:
Cohesin, acetyltransferase, Roberts syndrome, Sororin, DSB repair
Abstract:
Cohesin and cohesin regulatory proteins function in an essential pathway enabling proper cohesion and segregation of sister chromatids. Additionally, these proteins are involved in double-strand break (DSB) repair and transcriptional regulation. Mutations in establishment of cohesion 1 homolog 2 (Esco2), an evolutionary conserved cohesin acetyltransferase, are the cause of Roberts syndrome (RBS), a human congenital disorder. To explore the mechanism by which the deficiency in Esco2
affects cohesin’s functions, we generated
a mouse harboring a conditional Esco2
allele. To our surprise and in marked
contrast to RBS, mouse Esco2 turns out
to be a cell viability factor, the absence
of which results in severe chromosome
segregation defects and apoptosis. We
found that the acetylation of the cohesin subunit Smc3 is significantly reduced
in Esco2-deficient cells resulting in a
marked reduction of Sororin recruitment
to several, but not all cohesin bound loci.
Here, we provide evidence that Esco2 is
also required for DSB repair, which is
consistent with previous studies in RBS
cells.
