X-ray repair cross-complementing protein 6 selections

Search

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)

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: - belongs to the ku70 family - contains 1 Ku domain - contains 1 SAP domain Compartment: nucleus. chromosome 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

General

antigen helicase (DNA unwinding protein, DNA untwisting protein) phosphoprotein protein subunit

Properties

SIZE: entity length = 609 aa MW = 70 kD COMPARTMENT: cell nucleus MOTIF: serine-rich region {2-61} MOTIF: serine residue (SEVERAL) acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl Ser phosphorylation site {S6} acidic region {11-29} MOTIF: acidic residue (SEVERAL) Ser phosphorylation site {S27} lysine residue {K31} Ser phosphorylation site {S51} Ser phosphorylation site {S222} Ku {261-468} MOTIF: acidic region {330-342} MOTIF: acidic residue (SEVERAL) Thr phosphorylation site {T455} Ser phosphorylation site {S520} SAP {573-607}

References

UniProt :accession P12956
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: 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

Databases & Figures