X-ray repair cross-complementing protein 5; 86 kD subunit of Ku antigen; p86Ku; ATP-dependent DNA helicase 2 subunit 2; ATP-dependent DNA helicase II 80 kD subunit; CTC box-binding factor 85 kD subunit; CTC85; CTCBF; 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 (double-strand-break rejoining) (XRCC5, G22P2)
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Function
- single stranded DNA-dependent ATP-dependent helicase
- role in chromosome translocation
- the DNA helicase 2 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
- role in DNA non-homologous end joining (NHEJ) required for double-strand break repair & V(D)J recombination
- the XRCC5/6 dimer acts as a 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
- assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step
- in association with NAA15, the XRCC5/XRCC6 dimer binds to the osteocalcin promoter & activates osteocalcin expression
- the XRCC5/XRCC6 dimer probably acts as a 5'-deoxyribose-5-phosphate lyase, by catalyzing the beta-elimination of 5'-deoxyribose-5-phosphate at an abasic site near double-strand breaks
- XRCC5 probably acts as the catalytic subunit, removing abasic sites from the termini associated with DNA strand breaks, prior to ligation
- phosphorylated on Ser
- phosphorylation by PRKDC may enhance helicase activity
- sumoylated
- heterodimer of a 70 kD & a 80 kD subunit
- the 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 dimer also associates with NAA15,
- this complex displays DNA binding activity towards the osteocalcin FGF response element (OCFRE)
- the 80 kD subunit binds to the osteoblast-specific transcription factors MSX2 & RUNX2
- interacts with ELF3
- may interact with APLF
Structure
- the EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC & its recruitment to sites of DNA damage
- belongs to the ku80 family
- contains 1 Ku domain
Compartment
Expression
- expression increases during promyelocyte differentiation
- induced In osteoblasts, by FGF2
Pathology
- individuals with systemic lupus erythematosus (SLE) & related disorders produce extremely large amounts of autoantibodies to XRCC6 & XRCC5
More general terms
Component of
References
- ↑ UniProt http://www.uniprot.org/uniprot/P13010.html
- ↑ NIEHS SNPs http://egp.gs.washington.edu/data/xrcc5/
- ↑ 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