Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes.

ABSTRACT: Transcription hinders replication fork progression and stability. The ATR checkpoint and specialized DNA helicases assist DNA synthesis across transcription units to protect genome integrity. Combining genomic and genetic approaches together with the analysis of replication intermediates, we searched for factors coordinating replication with transcription. We show that the Sen1/Senataxin DNA/RNA helicase associates with forks, promoting their progression across RNA polymerase II (RNAPII)-transcribed genes. sen1 mutants accumulate aberrant DNA structures and DNA-RNA hybrids while forks clash head-on with RNAPII transcription units. These replication defects correlate with hyperrecombination and checkpoint activation in sen1 mutants. The Sen1 function at the forks is separable from its role

SUBMITTER: Alzu A 

PROVIDER: S-EPMC3494831 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature