Establishment of a replication fork barrier following induction of DNA binding in mammalian cells.

ABSTRACT: Understanding the mechanisms that lead to replication fork blocks (RFB) and the means to bypass them is important given the threat that they represent for genome stability if inappropriately handled. Here, to study this issue in mammals, we use integrated arrays of the LacO and/or TetO as a tractable system to follow in time a process in an individual cell and at a single locus. Importantly, we show that induction of the binding by LacI and TetR proteins, and not the presence of the repeats, is key to form the RFB. We find that the binding of the proteins to the arrays during replication causes a prolonged persistence of replication foci at the site. This, in turn, induces a local DNA damage repair (DDR) response, with the recruitment of proteins involved in double-strand break (DSB) repai

SUBMITTER: Beuzer P 

PROVIDER: S-EPMC4050166 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature