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

Marit E Geijer; Di Zhou; Kathiresan Selvam; Barbara Steurer; Chirantani Mukherjee; Bastiaan Evers; Simona Cugusi; Marvin van Toorn; Melanie van der Woude; Roel C Janssens; Yannick P Kok; Wenzhi Gong; Anja Raams; Calvin S Y Lo; Joyce H G Lebbink; Bart Geverts; Dalton A Plummer; Karel Bezstarosti; Arjan F Theil; Richard Mitter; Adriaan B Houtsmuller; Wim Vermeulen; Jeroen A A Demmers; Shisheng Li; Marcel A T M van Vugt; Hannes Lans; René Bernards; Jesper Q Svejstrup; Arnab Ray Chaudhuri; John J Wyrick; Jurgen A Marteijn

doi:10.1038/s41556-021-00692-z

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

Marit E Geijer, Di Zhou, Kathiresan Selvam, Barbara Steurer, Chirantani Mukherjee, Bastiaan Evers, Simona Cugusi, Marvin van Toorn, Melanie van der Woude, Roel C Janssens, Yannick P Kok, Wenzhi Gong, Anja Raams, Calvin S Y Lo, Joyce H G Lebbink, Bart Geverts, Dalton A Plummer, Karel Bezstarosti, Arjan F Theil, Richard MitterAdriaan B Houtsmuller, Wim Vermeulen, Jeroen A A Demmers, Shisheng Li, Marcel A T M van Vugt, Hannes Lans, René Bernards, Jesper Q Svejstrup, Arnab Ray Chaudhuri, John J Wyrick, Jurgen A Marteijn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	608-619
Number of pages	12
Journal	Nature Cell Biology
Volume	23
Issue number	6
DOIs	https://doi.org/10.1038/s41556-021-00692-z
Publication status	Published - 9-Jun-2021

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Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instabilityFinal publisher's version, 13.4 MBLicence: Taverne

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Geijer, M. E., Zhou, D., Selvam, K., Steurer, B., Mukherjee, C., Evers, B., Cugusi, S., van Toorn, M., van der Woude, M., Janssens, R. C., Kok, Y. P., Gong, W., Raams, A., Lo, C. S. Y., Lebbink, J. H. G., Geverts, B., Plummer, D. A., Bezstarosti, K., Theil, A. F., ... Marteijn, J. A. (2021). Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability. Nature Cell Biology, 23(6), 608-619. https://doi.org/10.1038/s41556-021-00692-z

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title = "Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability",

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.",

author = "Geijer, {Marit E} and Di Zhou and Kathiresan Selvam and Barbara Steurer and Chirantani Mukherjee and Bastiaan Evers and Simona Cugusi and {van Toorn}, Marvin and {van der Woude}, Melanie and Janssens, {Roel C} and Kok, {Yannick P} and Wenzhi Gong and Anja Raams and Lo, {Calvin S Y} and Lebbink, {Joyce H G} and Bart Geverts and Plummer, {Dalton A} and Karel Bezstarosti and Theil, {Arjan F} and Richard Mitter and Houtsmuller, {Adriaan B} and Wim Vermeulen and Demmers, {Jeroen A A} and Shisheng Li and {van Vugt}, {Marcel A T M} and Hannes Lans and Ren{\'e} Bernards and Svejstrup, {Jesper Q} and {Ray Chaudhuri}, Arnab and Wyrick, {John J} and Marteijn, {Jurgen A}",

year = "2021",

month = jun,

day = "9",

doi = "10.1038/s41556-021-00692-z",

language = "English",

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Geijer, ME, Zhou, D, Selvam, K, Steurer, B, Mukherjee, C, Evers, B, Cugusi, S, van Toorn, M, van der Woude, M, Janssens, RC, Kok, YP, Gong, W, Raams, A, Lo, CSY, Lebbink, JHG, Geverts, B, Plummer, DA, Bezstarosti, K, Theil, AF, Mitter, R, Houtsmuller, AB, Vermeulen, W, Demmers, JAA, Li, S, van Vugt, MATM, Lans, H, Bernards, R, Svejstrup, JQ, Ray Chaudhuri, A, Wyrick, JJ & Marteijn, JA 2021, 'Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability', Nature Cell Biology, vol. 23, no. 6, pp. 608-619. https://doi.org/10.1038/s41556-021-00692-z

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, René

AU - Svejstrup, Jesper Q

AU - Ray Chaudhuri, Arnab

AU - Wyrick, John J

AU - Marteijn, Jurgen A

PY - 2021/6/9

Y1 - 2021/6/9

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.

U2 - 10.1038/s41556-021-00692-z

DO - 10.1038/s41556-021-00692-z

M3 - Article

C2 - 34108662

SN - 1465-7392

VL - 23

SP - 608

EP - 619

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 6

ER -

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

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