Meiotic silencing of unpaired chromatin (MSUC) occurs during the first meiotic prophase, as chromosomes that fail to pair are sequestered into a transcriptionally-repressive nuclear domain. This phenomenon is exemplified by the heterologous sex chromosomes of male mammals, where the ATR DNA damage response kinase is critical for this silencing event. However, the mechanisms underlying the initiation of MSUC remain unknown. Here, we show that essential components of ATR signaling in somatic cells are spatially confined to unpaired chromosomes in spermatocytes, including the ATR-dependent phosphorylation of the single-stranded DNA (ssDNA) binding complex, Replication Protein A (RPA) and the checkpoint kinase, CHK1. These observations support a model where ssDNA plays a central role in the recruitment of ATR during MSUC, and a link to meiotic progression, through activation of CHK1.
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RESEARCH ARTICLE|
01 January 2015
Key mediators of somatic ATR signaling localize to unpaired chromosomes in spermatocytes
Andrew M. Fedoriw,
Andrew M. Fedoriw
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
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Debashish Menon,
Debashish Menon
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
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Yuna Kim,
Yuna Kim
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
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Weipeng Mu,
Weipeng Mu
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
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Terry Magnuson
Terry Magnuson
*
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
*Author for correspondence: trm4@med.unc.edu
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Andrew M. Fedoriw
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
Debashish Menon
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
Yuna Kim
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
Weipeng Mu
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
Terry Magnuson
*
Department of Genetics, Carolina Center for Genome Sciences
, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
, Chapel Hill, NC 27599
*Author for correspondence: trm4@med.unc.edu
Received:
13 May 2015
Accepted:
14 Jul 2015
Online ISSN: 1477-9129
Print ISSN: 0950-1991
© 2015. Published by The Company of Biologists Ltd
2015
Development dev.126078.
Article history
Received:
13 May 2015
Accepted:
14 Jul 2015
Currently Viewing Accepted Manuscript - Newer Version Available
01 Sep 2015
Citation
Andrew M. Fedoriw, Debashish Menon, Yuna Kim, Weipeng Mu, Terry Magnuson; Key mediators of somatic ATR signaling localize to unpaired chromosomes in spermatocytes. Development 2015; dev.126078. doi: https://doi.org/10.1242/dev.126078
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