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Sex chromosome inactivation in germ cells: emerging roles of DNA damage response pathways

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Abstract

Sex chromosome inactivation in male germ cells is a paradigm of epigenetic programming during sexual reproduction. Recent progress has revealed the underlying mechanisms of sex chromosome inactivation in male meiosis. The trigger of chromosome-wide silencing is activation of the DNA damage response (DDR) pathway, which is centered on the mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (γH2AX). This DDR pathway shares features with the somatic DDR pathway recognizing DNA replication stress in the S phase. Additionally, it is likely to be distinct from the DDR pathway that recognizes meiosis-specific double-strand breaks. This review article extensively discusses the underlying mechanism of sex chromosome inactivation.

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Acknowledgments

We thank Paul R. Andreassen and Yuya Ogawa for discussion and helpful comments regarding the manuscript. Y. I. is a research fellow of the Japan Society for the Promotion of Science. This work was supported by the Developmental Fund and Trustee Grant at Cincinnati Children’s Hospital Medical Center, the Basil O’Connor Award from the March of Dimes Foundation, and NIH Grant GM098605 to S.H.N.

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  1. Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Yosuke Ichijima, Ho-Su Sin & Satoshi H. Namekawa

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  1. Yosuke Ichijima
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  2. Ho-Su Sin
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  3. Satoshi H. Namekawa
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Correspondence to Satoshi H. Namekawa.

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Ichijima, Y., Sin, HS. & Namekawa, S.H. Sex chromosome inactivation in germ cells: emerging roles of DNA damage response pathways. Cell. Mol. Life Sci. 69, 2559–2572 (2012). https://doi.org/10.1007/s00018-012-0941-5

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  • DOI: https://doi.org/10.1007/s00018-012-0941-5

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