X-ray repair cross-complementing protein 5 selections

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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)

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: nucleus, chromosome 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

General

DNA-binding protein phosphoprotein protein subunit transcription factor (TF)

Properties

SIZE: entity length = 732 aa MW = 83 kD COMPARTMENT: cell nucleus MOTIF: leucine zipper SITE: 138-165 FOR-BINDING-VIA: leucine zipper Ku {251-460} MOTIF: Ser phosphorylation site {S258} proline-rich region SITE: 478-519 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S577} Ser phosphorylation site {S579} Ser phosphorylation site {S580} Thr phosphorylation site {T715} EEXXXDL {720-728}

References

UniProt :accession P13010
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: 8290597
Gottlieb TM, Jackson SP. Protein kinases and DNA damage. Trends Biochem Sci. 1994 Nov;19(11):500-3. Review. PMID: 7855895

Component-of

PRKDC complex

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