Cockayne syndrome B protein acts as an ATP-dependent processivity factor that helps RNA polymerase II overcome nucleosome barriers

Significance Cockayne syndrome group B (CSB) belongs to the SWI2/SNF2 family chromatin remodelers and plays critical roles in DNA damage response, repair, and gene expression. Despite its broad roles in gene expression, it has remained elusive whether and how CSB functions as a chromatin remodeler, a transcription elongation factor, or both, in regulating RNA polymerase II (Pol II) transcription on chromatin. Here, we reveal that Rad26, the yeast CSB ortholog, is recruited to the upstream of Pol II as an ATP-dependent processivity factor that assists Pol II in overcoming downstream nucleosome barriers during transcription. This paper provides mechanistic insights into the roles of CSB in different aspects of transcription and DNA repair on chromatin, including release of transcription pausing and elongation. While loss-of-function mutations in Cockayne syndrome group B protein (CSB) cause neurological diseases, this unique member of the SWI2/SNF2 family of chromatin remodelers has been broadly implicated in transcription elongation and transcription-coupled DNA damage repair, yet its mechanism remains largely elusive. Here, we use a reconstituted in vitro transcription system with purified polymerase II (Pol II) and Rad26, a yeast ortholog of CSB, to study the role of CSB in transcription elongation through nucleosome barriers. We show that CSB forms a stable complex with Pol II and acts as an ATP-dependent processivity factor that helps Pol II across a nucleosome barrier. This noncanonical mechanism is distinct from the canonical modes of chromatin remodelers that directly engage and remodel nucleosomes or transcription elongation factors that facilitate Pol II nucleosome bypass without hydrolyzing ATP. We propose a model where CSB facilitates gene expression by helping Pol II bypass chromatin obstacles while maintaining their structures.

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