The Mre11 complex in telomere maintenance

Sloan-Kettering Institute For Cancer Res, New York NY

Investigators

Abstract

DESCRIPTION (provided by applicant): The Mre 11 complex (Mrel 1, Rad50, and Nbsl) plays a central role in governing the cellular response to DNA damage and maintaining genomic stability. The diverse functions of the complex include the sensing of DNA damage, regulation of cell cycle checkpoints, and telomere maintenance. Mutations in the Nbsl and Mrel 1 genes cause the human diseases Nijmegen Breakage Syndrome (NBS) and Ataxia-telangiectasia like disease (A-TLD) which result in clastogen sensitivity and cancer predisposition. The role of the Mrel 1 complex in telomere metabolism and the status of these functions in NBS and A-TLD remain largely unexplored. I propose to use mouse models of NBS and A-TLD to examine the impact of Mre11 complex deficiency on telomere maintenance, and cancer development. I will 1) characterize the effects of Mre11 complex deficiency on telomere status, 2) determine the impact of Mrel I complex deficiency on the response telomere dysfunction and 3) analyze the genetic interactions of the Mre11 complex and determine their impact on telomere metabolism and the development of malignancy.