SCAI promotes DNA double-strand break repair in distinct chromosomal contexts

Publikation: Bidrag til tidsskriftLetterForskningfagfællebedømt

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SCAI promotes DNA double-strand break repair in distinct chromosomal contexts. / Hansen, Rebecca Kring; Mund, Andreas; Poulsen, Sara Lund; Sandoval, Maria; Klement, Karolin; Tsouroula, Katerina; Tollenaere, Maxim A X; Räschle, Markus; Soria, Rebeca; Offermanns, Stefan; Worzfeld, Thomas; Grosse, Robert; Brandt, Dominique T; Rozell, Björn; Mann, Matthias; Cole, Francesca; Soutoglou, Evi; Goodarzi, Aaron A; Daniel, Jeremy A; Mailand, Niels; Bekker-Jensen, Simon.

I: Nature Cell Biology, Bind 18, Nr. 12, 07.11.2016, s. 1357–1366.

Publikation: Bidrag til tidsskriftLetterForskningfagfællebedømt

Harvard

Hansen, RK, Mund, A, Poulsen, SL, Sandoval, M, Klement, K, Tsouroula, K, Tollenaere, MAX, Räschle, M, Soria, R, Offermanns, S, Worzfeld, T, Grosse, R, Brandt, DT, Rozell, B, Mann, M, Cole, F, Soutoglou, E, Goodarzi, AA, Daniel, JA, Mailand, N & Bekker-Jensen, S 2016, 'SCAI promotes DNA double-strand break repair in distinct chromosomal contexts', Nature Cell Biology, bind 18, nr. 12, s. 1357–1366. https://doi.org/10.1038/ncb3436

APA

Hansen, R. K., Mund, A., Poulsen, S. L., Sandoval, M., Klement, K., Tsouroula, K., Tollenaere, M. A. X., Räschle, M., Soria, R., Offermanns, S., Worzfeld, T., Grosse, R., Brandt, D. T., Rozell, B., Mann, M., Cole, F., Soutoglou, E., Goodarzi, A. A., Daniel, J. A., ... Bekker-Jensen, S. (2016). SCAI promotes DNA double-strand break repair in distinct chromosomal contexts. Nature Cell Biology, 18(12), 1357–1366. https://doi.org/10.1038/ncb3436

Vancouver

Hansen RK, Mund A, Poulsen SL, Sandoval M, Klement K, Tsouroula K o.a. SCAI promotes DNA double-strand break repair in distinct chromosomal contexts. Nature Cell Biology. 2016 nov 7;18(12):1357–1366. https://doi.org/10.1038/ncb3436

Author

Hansen, Rebecca Kring ; Mund, Andreas ; Poulsen, Sara Lund ; Sandoval, Maria ; Klement, Karolin ; Tsouroula, Katerina ; Tollenaere, Maxim A X ; Räschle, Markus ; Soria, Rebeca ; Offermanns, Stefan ; Worzfeld, Thomas ; Grosse, Robert ; Brandt, Dominique T ; Rozell, Björn ; Mann, Matthias ; Cole, Francesca ; Soutoglou, Evi ; Goodarzi, Aaron A ; Daniel, Jeremy A ; Mailand, Niels ; Bekker-Jensen, Simon. / SCAI promotes DNA double-strand break repair in distinct chromosomal contexts. I: Nature Cell Biology. 2016 ; Bind 18, Nr. 12. s. 1357–1366.

Bibtex

@article{7304de8cf8b44aa0927004d7b43611e1,
title = "SCAI promotes DNA double-strand break repair in distinct chromosomal contexts",
abstract = "DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions, whose accurate repair by non-homologous end-joining (NHEJ) or homologous recombination (HR) is crucial for genome integrity and is strongly influenced by the local chromatin environment. Here, we identify SCAI (suppressor of cancer cell invasion) as a 53BP1-interacting chromatin-associated protein that promotes the functionality of several DSB repair pathways in mammalian cells. SCAI undergoes prominent enrichment at DSB sites through dual mechanisms involving 53BP1-dependent recruitment to DSB-surrounding chromatin and 53BP1-independent accumulation at resected DSBs. Cells lacking SCAI display reduced DSB repair capacity, hypersensitivity to DSB-inflicting agents and genome instability. We demonstrate that SCAI is a mediator of 53BP1-dependent repair of heterochromatin-associated DSBs, facilitating ATM kinase signalling at DSBs in repressive chromatin environments. Moreover, we establish an important role of SCAI in meiotic recombination, as SCAI deficiency in mice leads to germ cell loss and subfertility associated with impaired retention of the DMC1 recombinase on meiotic chromosomes. Collectively, our findings uncover SCAI as a physiologically important component of both NHEJ- and HR-mediated pathways that potentiates DSB repair efficiency in specific chromatin contexts.",
author = "Hansen, {Rebecca Kring} and Andreas Mund and Poulsen, {Sara Lund} and Maria Sandoval and Karolin Klement and Katerina Tsouroula and Tollenaere, {Maxim A X} and Markus R{\"a}schle and Rebeca Soria and Stefan Offermanns and Thomas Worzfeld and Robert Grosse and Brandt, {Dominique T} and Bj{\"o}rn Rozell and Matthias Mann and Francesca Cole and Evi Soutoglou and Goodarzi, {Aaron A} and Daniel, {Jeremy A} and Niels Mailand and Simon Bekker-Jensen",
year = "2016",
month = nov,
day = "7",
doi = "10.1038/ncb3436",
language = "English",
volume = "18",
pages = "1357–1366",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "nature publishing group",
number = "12",

}

RIS

TY - JOUR

T1 - SCAI promotes DNA double-strand break repair in distinct chromosomal contexts

AU - Hansen, Rebecca Kring

AU - Mund, Andreas

AU - Poulsen, Sara Lund

AU - Sandoval, Maria

AU - Klement, Karolin

AU - Tsouroula, Katerina

AU - Tollenaere, Maxim A X

AU - Räschle, Markus

AU - Soria, Rebeca

AU - Offermanns, Stefan

AU - Worzfeld, Thomas

AU - Grosse, Robert

AU - Brandt, Dominique T

AU - Rozell, Björn

AU - Mann, Matthias

AU - Cole, Francesca

AU - Soutoglou, Evi

AU - Goodarzi, Aaron A

AU - Daniel, Jeremy A

AU - Mailand, Niels

AU - Bekker-Jensen, Simon

PY - 2016/11/7

Y1 - 2016/11/7

N2 - DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions, whose accurate repair by non-homologous end-joining (NHEJ) or homologous recombination (HR) is crucial for genome integrity and is strongly influenced by the local chromatin environment. Here, we identify SCAI (suppressor of cancer cell invasion) as a 53BP1-interacting chromatin-associated protein that promotes the functionality of several DSB repair pathways in mammalian cells. SCAI undergoes prominent enrichment at DSB sites through dual mechanisms involving 53BP1-dependent recruitment to DSB-surrounding chromatin and 53BP1-independent accumulation at resected DSBs. Cells lacking SCAI display reduced DSB repair capacity, hypersensitivity to DSB-inflicting agents and genome instability. We demonstrate that SCAI is a mediator of 53BP1-dependent repair of heterochromatin-associated DSBs, facilitating ATM kinase signalling at DSBs in repressive chromatin environments. Moreover, we establish an important role of SCAI in meiotic recombination, as SCAI deficiency in mice leads to germ cell loss and subfertility associated with impaired retention of the DMC1 recombinase on meiotic chromosomes. Collectively, our findings uncover SCAI as a physiologically important component of both NHEJ- and HR-mediated pathways that potentiates DSB repair efficiency in specific chromatin contexts.

AB - DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions, whose accurate repair by non-homologous end-joining (NHEJ) or homologous recombination (HR) is crucial for genome integrity and is strongly influenced by the local chromatin environment. Here, we identify SCAI (suppressor of cancer cell invasion) as a 53BP1-interacting chromatin-associated protein that promotes the functionality of several DSB repair pathways in mammalian cells. SCAI undergoes prominent enrichment at DSB sites through dual mechanisms involving 53BP1-dependent recruitment to DSB-surrounding chromatin and 53BP1-independent accumulation at resected DSBs. Cells lacking SCAI display reduced DSB repair capacity, hypersensitivity to DSB-inflicting agents and genome instability. We demonstrate that SCAI is a mediator of 53BP1-dependent repair of heterochromatin-associated DSBs, facilitating ATM kinase signalling at DSBs in repressive chromatin environments. Moreover, we establish an important role of SCAI in meiotic recombination, as SCAI deficiency in mice leads to germ cell loss and subfertility associated with impaired retention of the DMC1 recombinase on meiotic chromosomes. Collectively, our findings uncover SCAI as a physiologically important component of both NHEJ- and HR-mediated pathways that potentiates DSB repair efficiency in specific chromatin contexts.

U2 - 10.1038/ncb3436

DO - 10.1038/ncb3436

M3 - Letter

C2 - 27820601

VL - 18

SP - 1357

EP - 1366

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 12

ER -

ID: 169010589