Strand-specific effect of Rad26 and TFIIS in rescuing transcriptional arrest by CAG trinucleotide repeat slip-outs.

ABSTRACT: Transcription induced CAG repeat instability is associated with fatal neurological disorders. Genetic approaches found transcription-coupled nucleotide excision repair (TC-NER) factor CSB protein and TFIIS play critical roles in modulating the repeat stability. Here, we took advantage of an in vitro reconstituted yeast transcription system to investigate the underlying mechanism of RNA polymerase II (Pol II) transcriptional pausing/stalling by CAG slip-out structures and the functions of TFIIS and Rad26, the yeast ortholog of CSB, in modulating transcriptional arrest. We identified length-dependent and strand-specific mechanisms that account for CAG slip-out induced transcriptional arrest. We found substantial R-loop formation for the distal transcriptional pausing induced by template stra

SUBMITTER: Xu J 

PROVIDER: S-EPMC8287942 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature