Regulation of the DNA damage response on male meiotic sex chromosomes

Abstract

During meiotic prophase in males, the sex chromosomes partially synapse to form the XY body. This is 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. 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. However, the DNA damage response that spreads over the sex chromosomes is largely similar to that in somatic cells. Here we show that accumulation of some components of the DNA damage response pathway on the XY body occurs upstream of H2AX-MDC1-RNF8 signalling, and downstream from this cascade of events for others. 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.