PAF1C-driven restoration of RNAPII elongation after DNA damage occurs independently of transcription-associated histone mark deposition

DNA lesions block the progression of RNA polymerase II (RNAPII) during transcription, impeding gene expression and threatening genome integrity. When RNAPII stalls on transcription-blocking lesions, the transcription-coupled DNA repair pathway is activated to remove the DNA damage. Following DNA repair, efficient transcription restart depends on the PAF1 elongation complex (PAF1C). PAF1C contributes to deposition of transcription-associated histone marks, including H2B-K120 _Ub , H3K4me ₃ and H3K79me ₂ . These marks are enriched at actively transcribed genes and have been associated with regulation of post-repair transcription restart. Here, we show that the H2B-K120 E3 ubiquitin ligase RNF20/RNF40, the H3K4-methyltransferase SET1/COMPASS complex, and the H3K79-methyltransferase DOT1L are dispensable for transcription restart. Moreover, levels of H2B-K120 _Ub and H3K4me ₃ do not correlate with transcription restoration following DNA damage. Additionally, we observe that, unlike PAF1, the dissociable PAF1C subunit RTF1, while stimulating H2B-K120 _Ub and H3K4me ₃ , does not play a role in transcription restart. Together, these data suggest that transcription restoration after DNA damage is stimulated by the PAF1C elongation complex, independently of transcription-associated histone mark deposition.