Replication fork progression during re-replication requires the DNA damage checkpoint and double-strand break repair.

ABSTRACT: Replication origins are under tight regulation to ensure activation occurs only once per cell cycle [1, 2]. Origin re-firing in a single S phase leads to the generation of DNA double-strand breaks (DSBs) and activation of the DNA damage checkpoint [2-7]. If the checkpoint is blocked, cells enter mitosis with partially re-replicated DNA that generates chromosome breaks and fusions [5]. These types of chromosomal aberrations are common in numerous human cancers, suggesting that re-replication events contribute to cancer progression. It was proposed that fork instability and DSBs formed during re-replication are the result of head-to-tail collisions and collapse of adjacent replication forks [3]. However, previously studied systems lack the resolution to determine whether the observed DSBs ar

SUBMITTER: Alexander JL 

PROVIDER: S-EPMC4580973 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature