Regulation of the DNA damage response on male meiotic sex chromosomes

Nat Commun. 2013:4:2105. doi: 10.1038/ncomms3105.

Abstract

During meiotic prophase in males, the sex chromosomes partially synapse to form the XY body, a unique structure that recruits proteins involved in the DNA damage response, which is believed to be important for silencing of the sex chromosomes. It remains elusive how the DNA damage response in the XY body is regulated. Here we show that H2AX-MDC1-RNF8 signaling, which is well characterized in somatic cells, is dispensable for the recruitment of proteins to the unsynapsed axes in the XY body. On the other hand, the DNA damage response that spreads over the sex chromosomes is largely similar to that in somatic cells. This analysis shows that there are important differences between the regulation of the DNA damage response at the XY body and at DNA damage sites in somatic cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • BRCA1 Protein / chemistry
  • BRCA1 Protein / metabolism
  • Cell Cycle Proteins
  • Chromosome Pairing
  • DNA Damage*
  • DNA Repair
  • DNA-Activated Protein Kinase / metabolism
  • DNA-Binding Proteins / metabolism
  • Histones / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Meiosis*
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / metabolism
  • Pachytene Stage
  • Protein Structure, Tertiary
  • Protein Transport
  • Sex Chromosomes / metabolism*
  • Spermatocytes / cytology
  • Spermatocytes / metabolism
  • Sumoylation
  • Ubiquitin-Protein Ligases / deficiency
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Adaptor Proteins, Signal Transducing
  • BRCA1 Protein
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • MDC1 protein, mouse
  • Nuclear Proteins
  • gamma-H2AX protein, mouse
  • Rnf8 protein, mouse
  • Ubiquitin-Protein Ligases
  • Ataxia Telangiectasia Mutated Proteins
  • DNA-Activated Protein Kinase
  • Prkdc protein, mouse