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

First Author  Fedoriw AM Year  2015
Journal  Development Volume  142
Issue  17 Pages  2972-80
PubMed ID  26209650 Mgi Jnum  J:239795
Mgi Id  MGI:5829647 Doi  10.1242/dev.126078
Citation  Fedoriw AM, et al. (2015) Key mediators of somatic ATR signaling localize to unpaired chromosomes in spermatocytes. Development 142(17):2972-80
abstractText  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 crucial for this silencing event. However, the mechanisms underlying the initiation of MSUC remain unknown. Here, we show that essential components of ATR signaling in murine 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 in which ssDNA plays a central role in the recruitment of ATR during MSUC, and provide a link to meiotic progression through activation of CHK1.
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