Cellular and Molecular Life Sciences

, Volume 69, Issue 15, pp 2559–2572

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


DOI: 10.1007/s00018-012-0941-5

Cite this article as:
Ichijima, Y., Sin, H. & Namekawa, S.H. Cell. Mol. Life Sci. (2012) 69: 2559. doi:10.1007/s00018-012-0941-5


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.


Germ cellsMeiosisSex chromosomesDNA damage responseCheckpointEpigenetics

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Yosuke Ichijima
    • 1
  • Ho-Su Sin
    • 1
  • Satoshi H. Namekawa
    • 1
  1. 1.Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of MedicineCincinnatiUSA