A panorama of transcription-coupled repair in yeast chromatin

Abstract

Cyclobutane pyrimidine dimers (CPDs) are predominant ultraviolet (UV) light-induced DNA lesions that can result in mutations and lead to skin cancers (1). CPD lesions are primarily repaired by nucleotide excision repair (NER), a highly conserved repair pathway (2). NER consists of two subpathways: transcription-coupled NER (TC-NER) and global genome NER (GG-NER) (2). GG-NER can occur anywhere in the genome, whereas TC-NER is dedicated for repair of bulky lesions at transcribed strands of active genes (2). Eukaryotic TC-NER is initiated by stalled RNA polymerase II (Pol II) at DNA damage sites, whereas the damage recognition in GG-NER DNA is mainly achieved by repair factor XPC (2). Many factors can modulate the repair efficiency and outcome in vivo, including the chromatin organization and genomic location of lesions, accessibility of repair factors, and occupancy of repair facilitators and suppressors. In PNAS, Duan et al. (3) take a genomic approach to investigate how the genome-wide contribution of several key protein factors would impact the TC-NER process of CPDs in yeast, providing important insights into how TC-NER is modulated in yeast chromatin. In particular, Duan et al. (3) focus on three factors, Rad26, transcription factor IIH (TFIIH), and elongation factor Spt4/Spt5, that have dual roles in both TC-NER and transcription processes. During TC-NER, human Cockayne syndrome group B (CSB) protein and its yeast ortholog Rad26 play important roles in TC-NER. CSB/Rad26 is the first protein to be recruited to DNA damage-stalled Pol II (2). Human CSB, CSA, and UVSSA act cooperatively to recruit TFIIH to damage-stalled Pol II (4). TFIIH is involved in the lesion verification step as well as recruitment of repair factors for dual incision (2, 5). In contrast, yeast Spt4/Spt5 functions as a TC-NER suppressor and Rad26 is required to antagonize Spt4/Spt5’s suppression (6). Recent structure of the Pol II–Rad26 complex … [↵][1]1Email: dongwang{at}ucsd.edu. [1]: #xref-corresp-1-1