Title: Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability.
Authors: Geijer, Marit E; Zhou, Di; Selvam, Kathiresan; Steurer, Barbara; Mukherjee, Chirantani; Evers, Bastiaan; Cugusi, Simona; van Toorn, Marvin; van der Woude, Melanie; Janssens, Roel C; Kok, Yannick P; Gong, Wenzhi; Raams, Anja; Lo, Calvin S Y; Lebbink, Joyce H G; Geverts, Bart; Plummer, Dalton A; Bezstarosti, Karel; Theil, Arjan F; Mitter, Richard; Houtsmuller, Adriaan B; Vermeulen, Wim; Demmers, Jeroen A A; Li, Shisheng; van Vugt, Marcel A T M; Lans, Hannes; Bernards, René; Svejstrup, Jesper Q; Ray Chaudhuri, Arnab; Wyrick, John J; Marteijn, Jurgen A
Published In Nat Cell Biol, (2021 06)
Abstract: 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.
PubMed ID: 34108662
MeSH Terms: CRISPR-Cas Systems; Carrier Proteins/genetics; Carrier Proteins/metabolism; DNA Damage*; DNA Repair*; Evolution, Molecular; Genomic Instability*; HCT116 Cells; Humans; Peptide Elongation Factor 1/genetics; Peptide Elongation Factor 1/metabolism*; RNA Polymerase II/metabolism; Transcription Elongation, Genetic*; Transcription Factor TFIIH/genetics; Transcription Factor TFIIH/metabolism; Ubiquitination