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Description

X-ray repair cross-complementing protein 5 (UniProt: P13010, also known as 86 kDa subunit of Ku antigen, ATP-dependent DNA helicase 2 subunit 2, ATP-dependent DNA helicase II 80 kDa subunit, CTC box-binding factor 85 kDa subunit, CTC85, CTCBF,+D13 DNA repair protein XRCC5, Ku80, Ku86, Lupus Ku autoantigen protein p86, Nuclear factor IV, Thyroid-lupus autoantigen, TLAA, X-ray repair complementing defective repair in Chinese hamster cells 5) is encoded by the XRCC5 (also known as G22P2) gene (Gene ID: 7520) in human. XRCC5 is a single stranded DNA-dependent ATP-dependent helicase that exists as a heterodimer composed on XRCC5/XRCC6. This dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by about 100-fold. It plays a role in chromosome translocation. It binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It stabilizes broken DNA ends and bring them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ (Non-homologous end joining) ligation step. In association with NAA15, the XRCC5/6 dimer is shown to bind to the osteocalcin promoter and activates osteocalcin expression. The Ku domain of XRCC5 is localized in amino acids 251-260. It also contains an EEXXXDL motif (aa 720-728), which is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage. It undergoes phosphorylation on serine residues by PRKDC that enhances its helicase activity.