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MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response

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MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response. / Staples, Christopher J; Barone, Giancarlo; Myers, Katie N et al.
In: Cell, Vol. 16, No. 10, 06.09.2016, p. 2565-75.

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

HarvardHarvard

Staples, CJ, Barone, G, Myers, KN, Ganesh, A, Gibbs-Seymour, I, Patil, AA, Beveridge, RD, Daye, C, Beniston, R, Maslen, S, Ahel, I, Skehel, JM & Collis, SJ 2016, 'MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response', Cell, vol. 16, no. 10, pp. 2565-75. https://doi.org/10.1016/j.celrep.2016.07.087

APA

Staples, C. J., Barone, G., Myers, K. N., Ganesh, A., Gibbs-Seymour, I., Patil, A. A., Beveridge, R. D., Daye, C., Beniston, R., Maslen, S., Ahel, I., Skehel, J. M., & Collis, S. J. (2016). MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response. Cell, 16(10), 2565-75. https://doi.org/10.1016/j.celrep.2016.07.087

CBE

Staples CJ, Barone G, Myers KN, Ganesh A, Gibbs-Seymour I, Patil AA, Beveridge RD, Daye C, Beniston R, Maslen S, et al. 2016. MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response. Cell. 16(10):2565-75. https://doi.org/10.1016/j.celrep.2016.07.087

MLA

Staples, Christopher J et al. "MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response". Cell. 2016, 16(10). 2565-75. https://doi.org/10.1016/j.celrep.2016.07.087

VancouverVancouver

Staples CJ, Barone G, Myers KN, Ganesh A, Gibbs-Seymour I, Patil AA et al. MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response. Cell. 2016 Sept 6;16(10):2565-75. Epub 2016 Aug 25. doi: 10.1016/j.celrep.2016.07.087

Author

Staples, Christopher J ; Barone, Giancarlo ; Myers, Katie N et al. / MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response. In: Cell. 2016 ; Vol. 16, No. 10. pp. 2565-75.

RIS

TY - JOUR

T1 - MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response

AU - Staples, Christopher J

AU - Barone, Giancarlo

AU - Myers, Katie N

AU - Ganesh, Anil

AU - Gibbs-Seymour, Ian

AU - Patil, Abhijit A

AU - Beveridge, Ryan D

AU - Daye, Caroline

AU - Beniston, Richard

AU - Maslen, Sarah

AU - Ahel, Ivan

AU - Skehel, J Mark

AU - Collis, Spencer J

N1 - Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2016/9/6

Y1 - 2016/9/6

N2 - Through an RNAi-based screen for previously uncharacterized regulators of genome stability, we have identified the human protein C5orf45 as an important factor in preventing the accumulation of DNA damage in human cells. Here, we functionally characterize C5orf45 as a binding partner of the MRE11-RAD50-NBS1 (MRN) damage-sensing complex. Hence, we rename C5orf45 as MRNIP for MRN-interacting protein (MRNIP). We find that MRNIP is rapidly recruited to sites of DNA damage. Cells depleted of MRNIP display impaired chromatin loading of the MRN complex, resulting in reduced DNA end resection and defective ATM-mediated DNA damage signaling, a reduced ability to repair DNA breaks, and radiation sensitivity. Finally, we show that MRNIP phosphorylation on serine 115 leads to its nuclear localization, and this modification is required for MRNIP's role in promoting genome stability. Collectively, these data reveal that MRNIP is an important component of the human DNA damage response.

AB - Through an RNAi-based screen for previously uncharacterized regulators of genome stability, we have identified the human protein C5orf45 as an important factor in preventing the accumulation of DNA damage in human cells. Here, we functionally characterize C5orf45 as a binding partner of the MRE11-RAD50-NBS1 (MRN) damage-sensing complex. Hence, we rename C5orf45 as MRNIP for MRN-interacting protein (MRNIP). We find that MRNIP is rapidly recruited to sites of DNA damage. Cells depleted of MRNIP display impaired chromatin loading of the MRN complex, resulting in reduced DNA end resection and defective ATM-mediated DNA damage signaling, a reduced ability to repair DNA breaks, and radiation sensitivity. Finally, we show that MRNIP phosphorylation on serine 115 leads to its nuclear localization, and this modification is required for MRNIP's role in promoting genome stability. Collectively, these data reveal that MRNIP is an important component of the human DNA damage response.

KW - Journal Article

U2 - 10.1016/j.celrep.2016.07.087

DO - 10.1016/j.celrep.2016.07.087

M3 - Article

C2 - 27568553

VL - 16

SP - 2565

EP - 2575

JO - Cell

JF - Cell

SN - 0092-8674

IS - 10

ER -