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Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability.

Marit E GeijerDi ZhouKathiresan SelvamBarbara SteurerChirantani MukherjeeBastiaan EversSimona CugusiMarvin van ToornMelanie van der WoudeRoel C JanssensYannick P KokWenzhi GongAnja RaamsCalvin S Y LoJoyce H G LebbinkBart GevertsDalton A PlummerKarel BezstarostiArjan F TheilRichard MitterAdriaan B HoutsmullerWim VermeulenJeroen A A DemmersShisheng LiMarcel A T M van VugtHannes LansRené BernardsJesper Q SvejstrupArnab Ray ChaudhuriJohn J WyrickJurgen A Marteijn
Published in: Nature cell biology (2021)
Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA polymerase II, causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions. However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR-Cas9 screen, we identified the elongation factor ELOF1 as an important factor in the transcription stress response following DNA damage. We show that ELOF1 has an evolutionarily conserved role in transcription-coupled nucleotide excision repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair transcription-blocking lesions and resume transcription. Additionally, ELOF1 modulates transcription to protect cells against transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage via two distinct mechanisms.
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