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Publication : Phosphorylation of CDK2 on threonine 160 influences silencing of sex chromosome during male meiosis.

First Author  Wang L Year  2014
Journal  Biol Reprod Volume  90
Issue  6 Pages  138
PubMed ID  24759790 Mgi Jnum  J:212829
Mgi Id  MGI:5582330 Doi  10.1095/biolreprod.113.116624
Citation  Wang L, et al. (2014) Phosphorylation of CDK2 on threonine 160 influences silencing of sex chromosome during male meiosis. Biol Reprod 90(6):138
abstractText  In mammalian meiosis, the X and Y chromosomes are largely unsynapsed and transcriptionally silenced during the pachytene stage of meiotic prophase (meiotic sex chromosome inactivation), forming a specialized nuclear territory called sex or XY body. An increasing number of proteins and noncoding RNAs were found to localize to the sex body and take part in influencing expression of sex chromosome genes. Cyclin-dependent kinase 2 (Cdk2 (-/-)) spermatocytes show incomplete sex chromosome pairing. Here, we further showed that phosphorylation of CDK2 isoform 1 (p-CDK2(39) [39 kDa]) on threonine 160 localizes to the sites of asynapsis and the sex body, interacting with phosphorylated gamma-H2AX. Meanwhile, p-CDK2(39) is frequently mislocalized throughout the sex body, and meiotic sex chromosome inactivation is disrupted in PWKxC57BL/6J hybrid mice. Furthermore, pachytene spermatocytes treated with mevastatin (an inhibitor of p-CDK2) showed overexpression of sex chromosome-linked genes. Our results highlight an important role for p-CDK2(39) in influencing silencing of the sex chromosomes during male meiosis by interacting with gamma-H2AX.
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