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

Autor: Geijer ME; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Zhou D; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Selvam K; School of Molecular Biosciences, Washington State University, Pullman, WA, USA., Steurer B; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Mukherjee C; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Evers B; Oncode Institute, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Cugusi S; Mechanisms of Transcription Laboratory, The Francis Crick Institute, London, UK., van Toorn M; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., van der Woude M; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Janssens RC; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Kok YP; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Gong W; Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA., Raams A; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Lo CSY; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Lebbink JHG; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.; Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands., Geverts B; Erasmus Optical Imaging Center, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Plummer DA; School of Molecular Biosciences, Washington State University, Pullman, WA, USA., Bezstarosti K; Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands., Theil AF; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Mitter R; Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK., Houtsmuller AB; Erasmus Optical Imaging Center, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Vermeulen W; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Demmers JAA; Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands., Li S; Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA., van Vugt MATM; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Lans H; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Bernards R; Oncode Institute, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Svejstrup JQ; Mechanisms of Transcription Laboratory, The Francis Crick Institute, London, UK., Ray Chaudhuri A; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands., Wyrick JJ; School of Molecular Biosciences, Washington State University, Pullman, WA, USA., Marteijn JA; Department of Molecular Genetics, Oncode Institute, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. J.Marteijn@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2021 Jun; Vol. 23 (6), pp. 608-619. Date of Electronic Publication: 2021 Jun 09.
DOI: 10.1038/s41556-021-00692-z
Abstrakt: 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.
Databáze: MEDLINE
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