Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability
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Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability. / 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, Rene; Svejstrup, Jesper Q.; Ray Chaudhuri, Arnab; Wyrick, John J.; Marteijn, Jurgen A.
In: Nature Cell Biology, Vol. 23, No. 7, 07.2021, p. 608–619.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability
AU - Geijer, Marit E.
AU - Zhou, Di
AU - Selvam, Kathiresan
AU - Steurer, Barbara
AU - Mukherjee, Chirantani
AU - Evers, Bastiaan
AU - Cugusi, Simona
AU - van Toorn, Marvin
AU - van der Woude, Melanie
AU - Janssens, Roel C.
AU - Kok, Yannick P.
AU - Gong, Wenzhi
AU - Raams, Anja
AU - Lo, Calvin S. Y.
AU - Lebbink, Joyce H. G.
AU - Geverts, Bart
AU - Plummer, Dalton A.
AU - Bezstarosti, Karel
AU - Theil, Arjan F.
AU - Mitter, Richard
AU - Houtsmuller, Adriaan B.
AU - Vermeulen, Wim
AU - Demmers, Jeroen A. A.
AU - Li, Shisheng
AU - van Vugt, Marcel A. T. M.
AU - Lans, Hannes
AU - Bernards, Rene
AU - Svejstrup, Jesper Q.
AU - Ray Chaudhuri, Arnab
AU - Wyrick, John J.
AU - Marteijn, Jurgen A.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
UR - https://www.nature.com/articles/s41556-021-00720-y
U2 - 10.1038/s41556-021-00692-z
DO - 10.1038/s41556-021-00692-z
M3 - Journal article
VL - 23
SP - 608
EP - 619
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 7
ER -
ID: 331785660