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MRNIP is a replication fork protection factor

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MRNIP is a replication fork protection factor. / Bennett, Laura; Wilkie, Angharad; Antonopoulou, Effrosyni et al.
In: Science Advances, Vol. 6, No. 28, eaba5974, 10.07.2020.

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

HarvardHarvard

Bennett, L, Wilkie, A, Antonopoulou, E, Ceppi, I, Sanchez, A, Vernon, E, Gamble, A, Myers, KN, Collis, SJ, Cejka, P & Staples, C 2020, 'MRNIP is a replication fork protection factor', Science Advances, vol. 6, no. 28, eaba5974. https://doi.org/10.1126/sciadv.aba5974

APA

Bennett, L., Wilkie, A., Antonopoulou, E., Ceppi, I., Sanchez, A., Vernon, E., Gamble, A., Myers, K. N., Collis, S. J., Cejka, P., & Staples, C. (2020). MRNIP is a replication fork protection factor. Science Advances, 6(28), Article eaba5974. https://doi.org/10.1126/sciadv.aba5974

CBE

Bennett L, Wilkie A, Antonopoulou E, Ceppi I, Sanchez A, Vernon E, Gamble A, Myers KN, Collis SJ, Cejka P, et al. 2020. MRNIP is a replication fork protection factor. Science Advances. 6(28):Article eaba5974. https://doi.org/10.1126/sciadv.aba5974

MLA

Bennett, Laura et al. "MRNIP is a replication fork protection factor". Science Advances. 2020. 6(28). https://doi.org/10.1126/sciadv.aba5974

VancouverVancouver

Bennett L, Wilkie A, Antonopoulou E, Ceppi I, Sanchez A, Vernon E et al. MRNIP is a replication fork protection factor. Science Advances. 2020 Jul 10;6(28):eaba5974. doi: 10.1126/sciadv.aba5974

Author

Bennett, Laura ; Wilkie, Angharad ; Antonopoulou, Effrosyni et al. / MRNIP is a replication fork protection factor. In: Science Advances. 2020 ; Vol. 6, No. 28.

RIS

TY - JOUR

T1 - MRNIP is a replication fork protection factor

AU - Bennett, Laura

AU - Wilkie, Angharad

AU - Antonopoulou, Effrosyni

AU - Ceppi, Ilaria

AU - Sanchez, Aurore

AU - Vernon, Ellen

AU - Gamble, Amelia

AU - Myers, Katie N

AU - Collis, Spencer J

AU - Cejka, Petr

AU - Staples, Christopher

N1 - Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PY - 2020/7/10

Y1 - 2020/7/10

N2 - The remodeling of stalled replication forks to form four-way DNA junctions is an important component of the replication stress response. Nascent DNA at the regressed arms of these reversed forks is protected by RAD51 and the tumor suppressors BRCA1/2, and when this function is compromised, stalled forks undergo pathological MRE11-dependent degradation, leading to chromosomal instability. However, the mechanisms regulating MRE11 functions at reversed forks are currently unclear. Here, we identify the MRE11-binding protein MRNIP as a novel fork protection factor that directly binds to MRE11 and specifically represses its exonuclease activity. The loss of MRNIP results in impaired replication fork progression, MRE11 exonuclease–dependent degradation of reversed forks, persistence of underreplicated genomic regions, chemosensitivity, and chromosome instability. Our findings identify MRNIP as a novel regulator of MRE11 at reversed forks and provide evidence that regulation of specific MRE11 nuclease activities ensures protection of nascent DNA and thereby genome integrity.

AB - The remodeling of stalled replication forks to form four-way DNA junctions is an important component of the replication stress response. Nascent DNA at the regressed arms of these reversed forks is protected by RAD51 and the tumor suppressors BRCA1/2, and when this function is compromised, stalled forks undergo pathological MRE11-dependent degradation, leading to chromosomal instability. However, the mechanisms regulating MRE11 functions at reversed forks are currently unclear. Here, we identify the MRE11-binding protein MRNIP as a novel fork protection factor that directly binds to MRE11 and specifically represses its exonuclease activity. The loss of MRNIP results in impaired replication fork progression, MRE11 exonuclease–dependent degradation of reversed forks, persistence of underreplicated genomic regions, chemosensitivity, and chromosome instability. Our findings identify MRNIP as a novel regulator of MRE11 at reversed forks and provide evidence that regulation of specific MRE11 nuclease activities ensures protection of nascent DNA and thereby genome integrity.

U2 - 10.1126/sciadv.aba5974

DO - 10.1126/sciadv.aba5974

M3 - Article

C2 - 32832601

VL - 6

JO - Science Advances

JF - Science Advances

SN - 2375-2548

IS - 28

M1 - eaba5974

ER -