THE HMRE11 HRAD50 PROTEIN COMPLEX AND NIJMEGEN BREAKAGE SYNDROME - LINKAGE OF DOUBLE-STRAND BREAK REPAIR TO THE CELLULAR DNA-DAMAGE RESPONSE/

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder ch aracterized by increased cancer incidence, cell cycle checkpoint defec ts, and ionizing radiation sensitivity. We have isolated the gene enco ding p95, a member of the hMre11/hRad50 double-strand break repair com plex. The p95 gene mapped to 8q21.3, the region that contains the NBS locus, and p95 was absent from NBS cells established from NBS patients , p95 deficiency in these cells completely abrogates the formation of hMre11/hRad50 ionizing radiation-induced foci. Comparison of the p95 c DNA to the NBS1 cDNA indicated that the p95 gene and NBS1 are identica l. The implication of hMre11/hRad50/p95 protein complex in NBS reveals a direct molecular link between DSB repair and cell cycle checkpoint functions.