Homologous chromosomes move and rapidly initiate contact at the sites of double-strand breaks in genes in G₀-phase human cells

Abstract

We recently reported that homologous chromosomes make contact at the sites of double-strand breaks (DSBs) induced by ionizing radiation (IR) and the restriction endonuclease I-PpoI in G₀/G₁-phase somatic human cells. The contact involves short segments of homologous chromosomes and is centered on a DSB that occurs in a gene; contact does not occur at a DSB in intergenic DNA. Contact between homologous chromosomes is abrogated by inhibition of transcription and requires the kinase activity of ATM, but not DNA-PK. Here, we report additional insights into the mechanism underlying this novel phenomenon. We identify four patterns of homologous chromosome contact, and show that contact between homologous arms, but not centrosomes, is induced by IR. Significantly, we demonstrate that contact is induced by IR in non-proliferating, G₀-phase human cells derived from tissue explants. Finally, we show that contact between homologous chromosomes is detectable as early as 5 min after IR. These results point to the existence of a mechanism that rapidly localizes homologous chromosome arms at sites of DSBs in genes in G₀-phase human cells.