Report

CPD Damage Recognition by Transcribing RNA Polymerase II

See allHide authors and affiliations

Science  09 Feb 2007:
Vol. 315, Issue 5813, pp. 859-862
DOI: 10.1126/science.1135400

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Abstract

Cells use transcription-coupled repair (TCR) to efficiently eliminate DNA lesions such as ultraviolet light–induced cyclobutane pyrimidine dimers (CPDs). Here we present the structure-based mechanism for the first step in eukaryotic TCR, CPD-induced stalling of RNA polymerase (Pol) II. A CPD in the transcribed strand slowly passes a translocation barrier and enters the polymerase active site. The CPD 5′-thymine then directs uridine misincorporation into messenger RNA, which blocks translocation. Artificial replacement of the uridine by adenosine enables CPD bypass; thus, Pol II stalling requires CPD-directed misincorporation. In the stalled complex, the lesion is inaccessible, and the polymerase conformation is unchanged. This is consistent with nonallosteric recruitment of repair factors and excision of a lesion-containing DNA fragment in the presence of Pol II.

View Full Text