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 G0/G1-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 G0/G1-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.