DNA Damage during Meiosis Induces Chromatin Remodeling and Synaptonemal Complex Disassembly

SummaryDNA damage to the germline genome must be accurately repaired to ensure transmission of intact genetic information to following generations. Meiosis presents challenges to the DNA damage response (DDR) because it universally requires changes to chromosome structure that can affect DNA repair outcomes. We report the existence of a meiotic DDR at chromosome axes that results in chromatin remodeling, synaptonemal complex disassembly, and axis separation in response to irradiation at late pachytene stages in C. elegans. The axis component HTP-3 is required for germline acquisition of H2AacK5, an axis-specific chromatin mark that is DNA damage responsive. Irradiated wild-types show reduction of H2AacK5 and axis separation that are dependent on the acetyltransferase MYS-1/TIP60. Restoration of H2AacK5 levels requires ATM-1 kinase and correlates with resynapsis. We propose that the meiotic DDR involves early chromatin remodeling at chromosome axes to dismantle structures promoting interhomolog recombination and facilitate efficient nonhomolog-based repair before pachytene exit.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (390 K)Download as PowerPoint slideHighlights► Meiotic chromosome axes acquire specific H2AacK5 chromatin mark ► Irradiation (IR) induces H2AacK5 reduction and synaptonemal complex (SC) disassembly ► IR-induced reduction of H2AacK5 and SC disassembly are dependent on mys-1/TIP60 ► Restoration of H2AacK5 levels at axes and SC reassembly following IR requires ATM-1