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Publication : HnRNP A1 phosphorylated by VRK1 stimulates telomerase and its binding to telomeric DNA sequence.

First Author  Choi YH Year  2012
Journal  Nucleic Acids Res Volume  40
Issue  17 Pages  8499-518
PubMed ID  22740652 Mgi Jnum  J:199689
Mgi Id  MGI:5504351 Doi  10.1093/nar/gks634
Citation  Choi YH, et al. (2012) HnRNP A1 phosphorylated by VRK1 stimulates telomerase and its binding to telomeric DNA sequence. Nucleic Acids Res 40(17):8499-518
abstractText  The telomere integrity is maintained via replication machinery, telomere associated proteins and telomerase. Many telomere associated proteins are regulated in a cell cycle-dependent manner. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a single-stranded oligonucleotide binding protein, is thought to play a pivotal role in telomere maintenance. Here, we identified hnRNP A1 as a novel substrate for vaccinia-related kinase 1 (VRK1), a cell cycle regulating kinase. Phosphorylation by VRK1 potentiates the binding of hnRNP A1 to telomeric ssDNA and telomerase RNA in vitro and enhances its function for telomerase reaction. VRK1 deficiency induces a shortening of telomeres with an abnormal telomere arrangement and activation of DNA-damage signaling in mouse male germ cells. Together, our data suggest that VRK1 is required for telomere maintenance via phosphorylation of hnRNP A1, which regulates proteins associated with the telomere and telomerase RNA.
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