Segmental duplications arise from Pol32-dependent repair of broken forks through two alternative replication-based mechanisms.

ABSTRACT: The propensity of segmental duplications (SDs) to promote genomic instability is of increasing interest since their involvement in numerous human genomic diseases and cancers was revealed. However, the mechanism(s) responsible for their appearance remain mostly speculative. Here, we show that in budding yeast, replication accidents, which are most likely transformed into broken forks, play a causal role in the formation of SDs. The Pol32 subunit of the major replicative polymerase Poldelta is required for all SD formation, demonstrating that SDs result from untimely DNA synthesis rather than from unequal crossing-over. Although Pol32 is known to be required for classical (Rad52-dependant) break-induced replication, only half of the SDs can be attributed to this mechanism. The remaining SDs

SUBMITTER: Payen C 

PROVIDER: S-EPMC2518615 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature