Key mediators of somatic ATR signaling localize to unpaired chromosomes in spermatocytes

Abstract

Meiotic silencing of unpaired chromatin (MSUC) occurs during the first meiotic prophase, as chromosomes that fail to pair are sequestered into a transcriptionally-repressive nuclear domain. This phenomenon is exemplified by the heterologous sex chromosomes of male mammals, where the ATR DNA damage response kinase is critical for this silencing event. However, the mechanisms underlying the initiation of MSUC remain unknown. Here, we show that essential components of ATR signaling in somatic cells are spatially confined to unpaired chromosomes in spermatocytes, including the ATR-dependent phosphorylation of the single-stranded DNA (ssDNA) binding complex, Replication Protein A (RPA) and the checkpoint kinase, CHK1. These observations support a model where ssDNA plays a central role in the recruitment of ATR during MSUC, and a link to meiotic progression, through activation of CHK1.