A comprehensive mechanism for 5-carboxylcytosine-induced transcriptional pausing revealed by Markov state models.

ABSTRACT: RNA polymerase II (Pol II) surveils the genome, pausing as it encounters DNA lesions and base modifications and initiating signals for DNA repair among other important regulatory events. Recent work suggests that Pol II pauses at 5-carboxycytosine (5caC), an epigenetic modification of cytosine, because of a specific hydrogen bond between the carboxyl group of 5caC and a specific residue in fork loop 3 of Pol II. This hydrogen bond compromises productive NTP binding and slows down elongation. Apart from this specific interaction, the carboxyl group of 5caC can potentially interact with numerous charged residues in the cleft of Pol II. However, it is not clear how other interactions between Pol II and 5caC contribute to pausing. In this study, we use Markov state models (a type of kinetic ne

SUBMITTER: Konovalov KA 

PROVIDER: S-EPMC8191312 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature