53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination

Elsa Callen; Dali Zong; Wei Wu; Nancy Wong; Andre Stanlie; Momoko Ishikawa; Raphael Pavani; Lavinia C. Dumitrache; Andrea K. Byrum; Carlos Mendez-Dorantes; Paula Martinez; Andres Canela; Yaakov Maman; Amanda Day; Michael J. Kruhlak; Maria A. Blasco; Jeremy M. Stark; Nima Mosammaparast; Peter J. McKinnon; André Nussenzweig

doi:10.1016/j.molcel.2019.09.024

53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination

Elsa Callen, Dali Zong, Wei Wu, Nancy Wong, Andre Stanlie, Momoko Ishikawa, Raphael Pavani, Lavinia C. Dumitrache, Andrea K. Byrum, Carlos Mendez-Dorantes, Paula Martinez, Andres Canela, Yaakov Maman, Amanda Day, Michael J. Kruhlak, Maria A. Blasco, Jeremy M. Stark, Nima Mosammaparast, Peter J. McKinnon, André Nussenzweig

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

75 Scopus citations

Abstract

BRCA1 promotes 5′-3′ end resection and subsequently loads RAD51 onto 3′ single-stranded DNA to initiate homologous recombination. Callen et al. demonstrate that 53BP1 antagonizes both key steps in homologous recombination—end resection and RAD51 loading—that are coordinated by BRCA1.

Original language	English
Pages (from-to)	26-38.e7
Journal	Molecular Cell
Volume	77
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2019.09.024
State	Published - 2 Jan 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Funding

We thank Anthony Tubbs for comments on the paper; Jennifer Mehalko and Dom Esposito (Protein Expression Laboratory, Frederick National Laboratory for Cancer Research) for transgenic constructs; Karim Baktiar, Diana Haines, and Elijah Edmonson (Pathology/Histotechnology Laboratory, Frederick National Laboratory for Cancer Research) for rodent necropsy, pathology analysis, and imaging; Joseph Kalen and Nimit Patel (Small Animal Imaging Program, Frederick National Laboratory for Cancer Research) for X-ray computed tomography (CT) scan imaging; Jennifer Wise and Kelly Smith for assistance with animal work; Davide Robbiani and Kai Ge for antibodies; Dan Durocher for shieldin constructs; David Goldstein and the CCR Genomics core for sequencing support; and Neil Johnson for discussions. Research in the J.M.S. laboratory is supported by NIH grant R01CA197506. Research in the N.M. laboratory is supported by NIH grant R01 227001. The A.N. laboratory is supported by the Intramural Research Program of the NIH, an Ellison Medical Foundation Senior Scholar in Aging Award (AG-SS- 2633-11), the Department of Defense Idea Expansion (W81XWH-15-2-006) and Breakthrough (W81XWH-16-1-599) Awards, the Alex's Lemonade Stand Foundation Award, and an NIH Intramural FLEX Award. E.C. D.Z. N.W. A.S. M.I. R.P. L.C.D. A.K.B. C.M.-D. P.M. A.D. and M.J.K. designed and performed experiments; W.W. and Y.M. analyzed the data; A.C. M.A.B. J.M.S. N.M. P.J.M. and A.N. supervised and provided advice; E.C. D.Z. and A.N. wrote the manuscript with comments from the authors. The authors declare no competing interests. We thank Anthony Tubbs for comments on the paper; Jennifer Mehalko and Dom Esposito (Protein Expression Laboratory, Frederick National Laboratory for Cancer Research) for transgenic constructs; Karim Baktiar, Diana Haines, and Elijah Edmonson (Pathology/Histotechnology Laboratory, Frederick National Laboratory for Cancer Research) for rodent necropsy, pathology analysis, and imaging; Joseph Kalen and Nimit Patel (Small Animal Imaging Program, Frederick National Laboratory for Cancer Research) for X-ray computed tomography (CT) scan imaging; Jennifer Wise and Kelly Smith for assistance with animal work; Davide Robbiani and Kai Ge for antibodies; Dan Durocher for shieldin constructs; David Goldstein and the CCR Genomics core for sequencing support; and Neil Johnson for discussions. Research in the J.M.S. laboratory is supported by NIH grant R01CA197506 . Research in the N.M. laboratory is supported by NIH grant R01 227001 . The A.N. laboratory is supported by the Intramural Research Program of the NIH , an Ellison Medical Foundation Senior Scholar in Aging Award ( AG-SS- 2633-11 ), the Department of Defense Idea Expansion ( W81XWH-15-2-006 ) and Breakthrough ( W81XWH-16-1-599 ) Awards , the Alex’s Lemonade Stand Foundation Award , and an NIH Intramural FLEX Award .

Funders	Funder number
Department of Defense Idea Expansion	W81XWH-15-2-006, W81XWH-16-1-599
Joseph Kalen and Nimit Patel
Pathology/Histotechnology Laboratory
National Institutes of Health	R01 227001
National Cancer Institute	R01CA197506
Ellison Medical Foundation	AG-SS- 2633-11
Alex's Lemonade Stand Foundation for Childhood Cancer
Frederick National Laboratory for Cancer Research

Keywords

53BP1
BRCA1
PARPi
aging
cancer
homologous recombination
resection
shieldin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.molcel.2019.09.024

Cite this

Callen, E., Zong, D., Wu, W., Wong, N., Stanlie, A., Ishikawa, M., Pavani, R., Dumitrache, L. C., Byrum, A. K., Mendez-Dorantes, C., Martinez, P., Canela, A., Maman, Y., Day, A., Kruhlak, M. J., Blasco, M. A., Stark, J. M., Mosammaparast, N., McKinnon, P. J., & Nussenzweig, A. (2020). 53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination. Molecular Cell, 77(1), 26-38.e7. https://doi.org/10.1016/j.molcel.2019.09.024

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title = "53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination",

abstract = "BRCA1 promotes 5′-3′ end resection and subsequently loads RAD51 onto 3′ single-stranded DNA to initiate homologous recombination. Callen et al. demonstrate that 53BP1 antagonizes both key steps in homologous recombination—end resection and RAD51 loading—that are coordinated by BRCA1.",

keywords = "53BP1, BRCA1, PARPi, aging, cancer, homologous recombination, resection, shieldin",

author = "Elsa Callen and Dali Zong and Wei Wu and Nancy Wong and Andre Stanlie and Momoko Ishikawa and Raphael Pavani and Dumitrache, {Lavinia C.} and Byrum, {Andrea K.} and Carlos Mendez-Dorantes and Paula Martinez and Andres Canela and Yaakov Maman and Amanda Day and Kruhlak, {Michael J.} and Blasco, {Maria A.} and Stark, {Jeremy M.} and Nima Mosammaparast and McKinnon, {Peter J.} and Andr{\'e} Nussenzweig",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2020",

month = jan,

day = "2",

doi = "10.1016/j.molcel.2019.09.024",

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Callen, E, Zong, D, Wu, W, Wong, N, Stanlie, A, Ishikawa, M, Pavani, R, Dumitrache, LC, Byrum, AK, Mendez-Dorantes, C, Martinez, P, Canela, A, Maman, Y, Day, A, Kruhlak, MJ, Blasco, MA, Stark, JM, Mosammaparast, N, McKinnon, PJ & Nussenzweig, A 2020, '53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination', Molecular Cell, vol. 77, no. 1, pp. 26-38.e7. https://doi.org/10.1016/j.molcel.2019.09.024

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T1 - 53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination

AU - Callen, Elsa

AU - Zong, Dali

AU - Wu, Wei

AU - Wong, Nancy

AU - Stanlie, Andre

AU - Ishikawa, Momoko

AU - Pavani, Raphael

AU - Dumitrache, Lavinia C.

AU - Byrum, Andrea K.

AU - Mendez-Dorantes, Carlos

AU - Martinez, Paula

AU - Canela, Andres

AU - Maman, Yaakov

AU - Day, Amanda

AU - Kruhlak, Michael J.

AU - Blasco, Maria A.

AU - Stark, Jeremy M.

AU - Mosammaparast, Nima

AU - McKinnon, Peter J.

AU - Nussenzweig, André

PY - 2020/1/2

Y1 - 2020/1/2

N2 - BRCA1 promotes 5′-3′ end resection and subsequently loads RAD51 onto 3′ single-stranded DNA to initiate homologous recombination. Callen et al. demonstrate that 53BP1 antagonizes both key steps in homologous recombination—end resection and RAD51 loading—that are coordinated by BRCA1.

AB - BRCA1 promotes 5′-3′ end resection and subsequently loads RAD51 onto 3′ single-stranded DNA to initiate homologous recombination. Callen et al. demonstrate that 53BP1 antagonizes both key steps in homologous recombination—end resection and RAD51 loading—that are coordinated by BRCA1.

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KW - BRCA1

KW - PARPi

KW - aging

KW - cancer

KW - homologous recombination

KW - resection

KW - shieldin

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AN - SCOPUS:85076886017

SN - 1097-2765

VL - 77

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JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -

53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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