Failed gene conversion leads to extensive end processing and chromosomal rearrangements in fission yeast.

ABSTRACT: Loss of heterozygosity (LOH), a causal event in cancer and human genetic diseases, frequently encompasses multiple genetic loci and whole chromosome arms. However, the mechanisms by which such extensive LOH arises, and how it is suppressed in normal cells is poorly understood. We have developed a genetic system to investigate the mechanisms of DNA double-strand break (DSB)-induced extensive LOH, and its suppression, using a non-essential minichromosome, Ch(16), in fission yeast. We find extensive LOH to arise from a new break-induced mechanism of isochromosome formation. Our data support a model in which Rqh1 and Exo1-dependent end processing from an unrepaired DSB leads to removal of the broken chromosome arm and to break-induced replication of the intact arm from the centromere, a consid

SUBMITTER: Tinline-Purvis H 

PROVIDER: S-EPMC2776099 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature