Werner Syndrome Protein Is Regulated and Phosphorylated by DNA-dependent Protein Kinase *

摘要: DNA double-strand breaks (DSBs) are a highly mutagenic and potentially lethal damage that occurs in all organisms. Mammalian cells repair DSBs by homologous recombination non-homologous end joining, the latter requiring DNA-dependent protein kinase (DNA-PK). Werner syndrome is disorder characterized genomic instability, aging pathologies defective WRN, RecQ-like helicase with exonuclease activity. We show WRN interacts directly catalytic subunit of DNA-PK (DNA-PKCS), which inhibits both activities WRN. In addition we forms stable complex on DNA-PKCS binding Ku. This assembly reverses enzymatic inhibition. Finally, phosphorylated vitro requires for phosphorylation vivo, deficient mildly sensitive to ionizing radiation. These data suggest may function together metabolism implicate joining.