X-ray repair cross-complementing protein 6; 5'-deoxyribose-5-phosphate lyase Ku70; 5'-dRP lyase Ku70; 70 kD subunit of Ku antigen; ATP-dependent DNA helicase 2 subunit 1; ATP-dependent DNA helicase II 70 kD subunit; CTC box-binding factor 75 kD subunit; CTC75; CTCBF; DNA repair protein XRCC6; Lupus Ku autoantigen protein p70; Ku70; thyroid-lupus autoantigen; TLAA; X-ray repair complementing defective repair in chinese hamster cells 6 (XRCC6, G22P1)
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Function
- single stranded DNA-dependent ATP-dependent helicase
- role in chromosome translocation
- the DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA (cell cycle-dependent)
- it works in the 3'-5' direction
- involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair & V(D)J recombination
- the XRCC5/XRCC6 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/XRCC6 dimer is probably involved in stabilizing broken DNA ends & bringing them together
- the assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step
- required for osteocalcin gene expression
- the XRCC5/XRCC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase, catalyzing the beta-elimination of 5'-deoxyribose-5-phosphate at an abasic site near DNA double-strand breaks
- XRCC5 probably acts as the catalytic subunit, removing abasic sites from the termini associated with DNA strand breaks, prior to ligation
- phosphorylation by PRKDC may enhance helicase activity
- phosphorylation of Ser-51 does not affect DNA repair
- heterodimer of a 70 kD (XRCC6) & a 80 kD (XRCC5) subuni
- the XRCC5/XRCC6 dimer associates in a DNA-dependent manner with PRKDC to form the DNA-dependent protein kinase complex DNA-PK, & with the LIG4-XRCC4 complex
- the XRCC5/XRCC6 dimer also associates with NAA15, & this complex binds to the osteocalcin promoter & activates osteocalcin expression
- in addition, XRCC6 interacts with the osteoblast-specific transcription factors MSX2, RUNX2 & DLX5
- interacts with ELF3
- interacts with XRCC6BP1
Structure
Compartment
Expression
- in contrast to XRCC5, expression does not increase during promyelocyte differentiation
- induced In osteoblasts, by FGF2
Pathology
- individuals with systemic lupus erythematosus (SLE) & related disorders produce extremely large amounts of autoantibodies to XRCC5 & XRCC6
- existence of a major autoantigenic epitope or epitopes on the C-terminal 190 amino acids of XRCC6 containing the leucine repeat
- the majority of autoantibodies to XRCC6 in most sera from patients with SLE seem to be reactive with this region
More general terms
Component of
References
- ↑ UniProt http://www.uniprot.org/uniprot/P12956.html
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/g22p1/
- ↑ Hoff CM, Ghosh AK, Prabhakar BS, Jacob ST. Enhancer 1 binding factor, a Ku-related protein, is a positive regulator of RNA polymerase I transcription initiation. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):762-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8290597
- ↑ Gottlieb TM, Jackson SP. Protein kinases and DNA damage. Trends Biochem Sci. 1994 Nov;19(11):500-3. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7855895