XRCC5 Antibody – Mouse Monoclonal

The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

Function: Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 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 100-fold. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. The XRCC5/6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription. Ref.9 Ref.13 Ref.17 Ref.25

Subunit structure: Heterodimer of a 70 kDa and a 80 kDa subunit. The dimer associates in a DNA-dependent manner with PRKDC to form the DNA-dependent protein kinase complex DNA-PK, and with the LIG4-XRCC4 complex. The dimer also associates with NAA15, and this complex displays DNA binding activity towards the osteocalcin FGF response element (OCFRE). In addition, the 80 kDa subunit binds to the osteoblast-specific transcription factors MSX2 and RUNX2. Interacts with ELF3. May interact with APLF. The XRCC5/6 dimer associates in a DNA-dependent manner with APEX1. Identified in a complex with DEAF1 and XRCC6. Ref.13 Ref.17 Ref.18 Ref.21 Ref.22 Ref.28

Subcellular location: Nucleus. Nucleus › nucleolus. Chromosome Ref.27 Ref.28.

Developmental stage: Expression increases during promyelocyte differentiation. Ref.10

Induction: In osteoblasts, by FGF2.

Domain: The EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage. Ref.20

Post-translational modification: Phosphorylated on serine residues. Phosphorylation by PRKDC may enhance helicase activity. Ref.16Sumoylated. Ref.19Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination following DNA damage, leading to its degradation and removal from DNA damage sites. Ref.29

Miscellaneous: Individuals with systemic lupus erythematosus (SLE) and related disorders produce extremely large amounts of autoantibodies to XRCC6 and XRCC5.

Sequence similarities: Belongs to the ku80 family.Contains 1 Ku domain.