1jey

Structural highlights

Function

[XRCC5_HUMAN] 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.^{[1] [2] [3] [4]} [XRCC6_HUMAN] 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. Required for osteocalcin gene expression. 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. 5'-dRP lyase activity 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.^{[5] [6] [7] [8] [9] [10] [11]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Tuteja N, Tuteja R, Ochem A, Taneja P, Huang NW, Simoncsits A, Susic S, Rahman K, Marusic L, Chen J, et al.. Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen. EMBO J. 1994 Oct 17;13(20):4991-5001. PMID:7957065
2. ↑ Chung U, Igarashi T, Nishishita T, Iwanari H, Iwamatsu A, Suwa A, Mimori T, Hata K, Ebisu S, Ogata E, Fujita T, Okazaki T. The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium. J Biol Chem. 1996 Apr 12;271(15):8593-8. PMID:8621488
3. ↑ Willis DM, Loewy AP, Charlton-Kachigian N, Shao JS, Ornitz DM, Towler DA. Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex. J Biol Chem. 2002 Oct 4;277(40):37280-91. Epub 2002 Jul 26. PMID:12145306 doi:http://dx.doi.org/10.1074/jbc.M206482200
4. ↑ Roberts SA, Strande N, Burkhalter MD, Strom C, Havener JM, Hasty P, Ramsden DA. Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends. Nature. 2010 Apr 22;464(7292):1214-7. doi: 10.1038/nature08926. Epub 2010 Apr 11. PMID:20383123 doi:http://dx.doi.org/10.1038/nature08926
5. ↑ Reeves WH, Sthoeger ZM. Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen. J Biol Chem. 1989 Mar 25;264(9):5047-52. PMID:2466842
6. ↑ Chung U, Igarashi T, Nishishita T, Iwanari H, Iwamatsu A, Suwa A, Mimori T, Hata K, Ebisu S, Ogata E, Fujita T, Okazaki T. The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium. J Biol Chem. 1996 Apr 12;271(15):8593-8. PMID:8621488
7. ↑ Tuteja N, Tuteja R, Ochem A, Taneja P, Huang NW, Simoncsits A, Susic S, Rahman K, Marusic L, Chen J, et al.. Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen. EMBO J. 1994 Oct 17;13(20):4991-5001. PMID:7957065
8. ↑ West RB, Yaneva M, Lieber MR. Productive and nonproductive complexes of Ku and DNA-dependent protein kinase at DNA termini. Mol Cell Biol. 1998 Oct;18(10):5908-20. PMID:9742108
9. ↑ Willis DM, Loewy AP, Charlton-Kachigian N, Shao JS, Ornitz DM, Towler DA. Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex. J Biol Chem. 2002 Oct 4;277(40):37280-91. Epub 2002 Jul 26. PMID:12145306 doi:http://dx.doi.org/10.1074/jbc.M206482200
10. ↑ Liu H, Herrmann CH, Chiang K, Sung TL, Moon SH, Donehower LA, Rice AP. 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. Biochem Biophys Res Commun. 2010 Jun 25;397(2):245-50. doi:, 10.1016/j.bbrc.2010.05.092. Epub 2010 May 20. PMID:20493174 doi:10.1016/j.bbrc.2010.05.092
11. ↑ Roberts SA, Strande N, Burkhalter MD, Strom C, Havener JM, Hasty P, Ramsden DA. Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends. Nature. 2010 Apr 22;464(7292):1214-7. doi: 10.1038/nature08926. Epub 2010 Apr 11. PMID:20383123 doi:http://dx.doi.org/10.1038/nature08926
12. ↑ Walker JR, Corpina RA, Goldberg J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature. 2001 Aug 9;412(6847):607-14. PMID:11493912 doi:10.1038/35088000