DNA damage signaling regulates cohesin stabilization and promotes meiotic chromosome axis morphogenesis

Abstract

A hallmark of meiosis is the reorganization of chromosomes as linear arrays of chromatin loops around a chromosome axis comprised of cohesins and regulatory proteins. Defective axis morphogenesis impairs homolog pairing, synapsis, and recombination. We find that axis assembly in C. elegans is promoted by DNA Damage Response (DDR) signaling activated at meiotic entry. Central to this regulation is downregulation of the cohesin release factor WAPL-1 by the DDR transducer kinase ATM-1, which is activated by the meiotic kinase CHK-2. Additional cohesin regulators, including ECO-1 and PDS-5, also contribute to stabilizing axis-associated cohesins. We find that downregulation of WAPL by ATM also promotes cohesin enrichment at DNA damage foci in cultured mammalian cells. Our findings reveal that the DDR and Wapl play conserved roles in cohesin regulation in meiotic prophase and proliferating cells. One-Sentence SummaryDNA Damage Response kinase ATM phosphorylates WAPL to promote meiotic chromosome axis assembly and DNA repair