title: 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 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.
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fedoriw
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Debashish
authors.initials: D
authors.lastname: Menon
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Mu
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA trm4@med.unc.edu.
authors.forename: Terry
authors.initials: T
authors.lastname: Magnuson
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002478:Cells, Cultured; D000071877:Checkpoint Kinase 1; D002843:Chromatin / Q000378:metabolism; D023902:Chromosome Pairing; D033481:Chromosomes, Mammalian / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004706:Endodeoxyribonucleases / Q000172:deficiency / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D021381:Protein Transport; D051716:Replication Protein A / Q000378:metabolism; D012730:Sex Chromosomes / Q000378:metabolism; D015398:Signal Transduction; D013090:Spermatocytes / Q000378:metabolism*; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D000071877:Checkpoint Kinase 1; D002843:Chromatin; D004706:Endodeoxyribonucleases; D010768:Phosphoserine; D011494:Protein Kinases; D051716:Replication Protein A; D000099257:Meiotic Recombination Protein SPO11; C576897:Atr protein, mouse; C000605869:Chek1 protein, mouse
keywords: CHEK1; Meiosis; Mouse; Spermatogenesis; Transcriptional regulation