DNA slip-outs cause RNA polymerase II arrest in vitro: potential implications for genetic instability.

ABSTRACT: The abnormal number of repeats found in triplet repeat diseases arises from 'repeat instability', in which the repetitive section of DNA is subject to a change in copy number. Recent studies implicate transcription in a mechanism for repeat instability proposed to involve RNA polymerase II (RNAPII) arrest caused by a CTG slip-out, triggering transcription-coupled repair (TCR), futile cycles of which may lead to repeat expansion or contraction. In the present study, we use defined DNA constructs to directly test whether the structures formed by CAG and CTG repeat slip-outs can cause transcription arrest in vitro. We found that a slip-out of (CAG)(20) or (CTG)(20) repeats on either strand causes RNAPII arrest in HeLa cell nuclear extracts. Perfect hairpins and loops on either strand also cau

SUBMITTER: Salinas-Rios V 

PROVIDER: S-EPMC3177194 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature