Nuclear myosin/actin-motored contact between homologous chromosomes is initiated by ATM kinase and homology-directed repair proteins at double-strand DNA breaks to suppress chromosome rearrangements

We provide evidence for a mechanism of DNA repair that requires nuclear myosin/actin-dependent contact between homologous chromosomes to prevent formation of chromosomal rearrangement in human cells. We recently showed that DNA double strand breaks (DSBs) induced by γ-rays or endonucleases cause ATM-dependent contact formation between homologous chromosomes at damaged sites of transcriptionally active chromatin in G(0)/G(1)-phase cells. Here, we report that the mechanism of contact generation between homologous chromosomes also requires homology-directed repair proteins, including BRCA1, RAD51 and RAD52, and nuclear myosin/actin-motors. Moreover, inhibition of ATM kinase or deficiency in nuclear actin polymerization causes carcinogenic RET/PTC chromosome rearrangements after DSBs induction in human cells. These data suggest that DSBs in transcriptionally active euchromatin in G(0)/G(1)-phase cells are repaired through a mechanism that requires contact formation between homologous chromosomes and that this mechanism is mediated by HDR proteins and nuclear myosin/actin motors.