HMRE11 AND HRAD50 NUCLEAR FOCI ARE INDUCED DURING THE NORMAL CELLULAR-RESPONSE TO DNA DOUBLE-STRAND BREAKS

We previously identified a conserved multiprotein complex that include s hMre11 and hRad50. In this study, we used immunofluorescence to inve stigate the role of this complex in DNA double-strand break (DSB) repa ir. hMre11 and hRad50 form discrete nuclear foci in response to treatm ent with DSB-inducing agents but not in response to UV irradiation. hM re11 and hRad50 foci colocalize after treatment with ionizing radiatio n and are distinct from those of the DSB repair protein, hRad51. Our d ata indicate that an irradiated cell is competent to form either hMre1 1-hRad50 foci or hRad51 foci, but not both. The multiplicity of hMre11 and hRad50 foci is much higher in the DSB repair-deficient cell line 180BR than in repair-proficient cells. hMre11-hRad50 focus formation i s markedly reduced in cells derived from ataxia-telangiectasia patient s, whereas hRad51 focus Formation is markedly increased. These experim ents support genetic evidence from Saccharomyces cerevisiae indicating that Mre11-Rad50 have roles distinct from that of Rad51 in DSB repair . Further, these data indicate that hMre11-hRad50 foci form in respons e to DNA DSBs and are dependent upon a DNA damage-induced signaling pa thway.