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BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis

During meiosis, DNA damage response (DDR) proteins induce transcriptional silencing of unsynapsed chromatin, including the constitutively unsynapsed XY chromosomes in males. DDR proteins are also implicated in double strand break repair during meiotic recombination. Here, we address the function of...

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Autores principales: Broering, Tyler J., Alavattam, Kris G., Sadreyev, Ruslan I., Ichijima, Yosuke, Kato, Yasuko, Hasegawa, Kazuteru, Camerini-Otero, R. Daniel, Lee, Jeannie T., Andreassen, Paul R., Namekawa, Satoshi H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050732/
https://www.ncbi.nlm.nih.gov/pubmed/24914237
http://dx.doi.org/10.1083/jcb.201311050
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author Broering, Tyler J.
Alavattam, Kris G.
Sadreyev, Ruslan I.
Ichijima, Yosuke
Kato, Yasuko
Hasegawa, Kazuteru
Camerini-Otero, R. Daniel
Lee, Jeannie T.
Andreassen, Paul R.
Namekawa, Satoshi H.
author_facet Broering, Tyler J.
Alavattam, Kris G.
Sadreyev, Ruslan I.
Ichijima, Yosuke
Kato, Yasuko
Hasegawa, Kazuteru
Camerini-Otero, R. Daniel
Lee, Jeannie T.
Andreassen, Paul R.
Namekawa, Satoshi H.
author_sort Broering, Tyler J.
collection PubMed
description During meiosis, DNA damage response (DDR) proteins induce transcriptional silencing of unsynapsed chromatin, including the constitutively unsynapsed XY chromosomes in males. DDR proteins are also implicated in double strand break repair during meiotic recombination. Here, we address the function of the breast cancer susceptibility gene Brca1 in meiotic silencing and recombination in mice. Unlike in somatic cells, in which homologous recombination defects of Brca1 mutants are rescued by 53bp1 deletion, the absence of 53BP1 did not rescue the meiotic failure seen in Brca1 mutant males. Further, BRCA1 promotes amplification and spreading of DDR components, including ATR and TOPBP1, along XY chromosome axes and promotes establishment of pericentric heterochromatin on the X chromosome. We propose that BRCA1-dependent establishment of X-pericentric heterochromatin is critical for XY body morphogenesis and subsequent meiotic progression. In contrast, BRCA1 plays a relatively minor role in meiotic recombination, and female Brca1 mutants are fertile. We infer that the major meiotic role of BRCA1 is to promote the dramatic chromatin changes required for formation and function of the XY body.
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spelling pubmed-40507322014-12-09 BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis Broering, Tyler J. Alavattam, Kris G. Sadreyev, Ruslan I. Ichijima, Yosuke Kato, Yasuko Hasegawa, Kazuteru Camerini-Otero, R. Daniel Lee, Jeannie T. Andreassen, Paul R. Namekawa, Satoshi H. J Cell Biol Research Articles During meiosis, DNA damage response (DDR) proteins induce transcriptional silencing of unsynapsed chromatin, including the constitutively unsynapsed XY chromosomes in males. DDR proteins are also implicated in double strand break repair during meiotic recombination. Here, we address the function of the breast cancer susceptibility gene Brca1 in meiotic silencing and recombination in mice. Unlike in somatic cells, in which homologous recombination defects of Brca1 mutants are rescued by 53bp1 deletion, the absence of 53BP1 did not rescue the meiotic failure seen in Brca1 mutant males. Further, BRCA1 promotes amplification and spreading of DDR components, including ATR and TOPBP1, along XY chromosome axes and promotes establishment of pericentric heterochromatin on the X chromosome. We propose that BRCA1-dependent establishment of X-pericentric heterochromatin is critical for XY body morphogenesis and subsequent meiotic progression. In contrast, BRCA1 plays a relatively minor role in meiotic recombination, and female Brca1 mutants are fertile. We infer that the major meiotic role of BRCA1 is to promote the dramatic chromatin changes required for formation and function of the XY body. The Rockefeller University Press 2014-06-09 /pmc/articles/PMC4050732/ /pubmed/24914237 http://dx.doi.org/10.1083/jcb.201311050 Text en © 2014 Broering et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Broering, Tyler J.
Alavattam, Kris G.
Sadreyev, Ruslan I.
Ichijima, Yosuke
Kato, Yasuko
Hasegawa, Kazuteru
Camerini-Otero, R. Daniel
Lee, Jeannie T.
Andreassen, Paul R.
Namekawa, Satoshi H.
BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis
title BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis
title_full BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis
title_fullStr BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis
title_full_unstemmed BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis
title_short BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis
title_sort brca1 establishes dna damage signaling and pericentric heterochromatin of the x chromosome in male meiosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050732/
https://www.ncbi.nlm.nih.gov/pubmed/24914237
http://dx.doi.org/10.1083/jcb.201311050
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