HUMAN RAD50 IS PHYSICALLY ASSOCIATED WITH HUMAN MRE11 - IDENTIFICATION OF A CONSERVED MULTIPROTEIN COMPLEX IMPLICATED IN RECOMBINATIONAL DNA-REPAIR

In this report, we describe the identification and molecular character ization of a human RAD50 homolog, hRAD50. hRAD50 was included in a col lection of cDNAs which were isolated by a direct cDNA selection strate gy focused on the chromosomal interval spanning 5q23 to 5q31. Alterati ons of the 5q23-q31 interval are frequently observed in myelodysplasia and myeloid leukemia. This strategy was thus undertaken to create a d etailed genetic map of that region. Saccharomyces cerevisiae RAD50 (Sc RAD50) is one of three yeast RAD52 epistasis group members (ScRAD50, S cMRE11, and ScXRS2) in which mutations eliminate meiotic recombination but confer a hyperrecombinational phenotype in mitotic cells. The yea st Rad50, Mre11, and Xrs2 proteins appear to act in a multiprotein com plex, consistent with the observation that the corresponding mutants c onfer essentially identical phenotypes. In this report, we demonstrate that the human Rad50 and Mre11 proteins are stably associated in a pr otein complex which may include three other proteins. hRAD50 is expres sed in all tissues examined, but mRNA levels are significantly higher in the testis. Other human RAD52 epistasis group homologs exhibit this expression pattern, suggesting the involvement of human RAD52 epistas is group proteins in meiotic recombination. Human RAD52 epistasis grou p proteins are highly conserved and act in protein complexes that are analogous to those of their yeast counterparts. These findings indicat e that the function of the RAD52 epistasis group is conserved in human cells.