XPA explained
DNA repair protein complementing XP-A cells is a protein that in humans is encoded by the XPA gene.[1]
Function
Nucleotide excision repair (NER) is a major pathway for repairing a variety of bulky DNA damages including those introduced by UV irradiation. The XPA protein appears to play a key role in NER at sites of damage as a scaffold for other repair proteins in order to ensure that the damages are appropriately excised.[2] Among the repair proteins with which XPA interacts is a protein complex (including the ERCC1 protein) that is capable of incising DNA at sites of damage.
Xpa mutant individuals often show the severe clinical symptoms of xeroderma pigmentosum, a condition involving extreme sensitivity to sunlight and a high incidence of skin cancer.
Interactions
XPA has been shown to interact with ERCC1,[3] [4] Replication protein A1[5] and XAB2.[6]
Further reading
- Cleaver JE, Thompson LH, Richardson AS, States JC . A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy . Human Mutation . 14 . 1 . 9–22 . 1999 . 10447254 . 10.1002/(SICI)1098-1004(1999)14:1<9::AID-HUMU2>3.0.CO;2-6 . 24148589 . free .
- Morikawa K, Shirakawa M . Three-dimensional structural views of damaged-DNA recognition: T4 endonuclease V, E. coli Vsr protein, and human nucleotide excision repair factor XPA . Mutation Research . 460 . 3–4 . 257–75 . Aug 2000 . 10946233 . 10.1016/s0921-8777(00)00031-8 .
- Satokata I, Tanaka K, Okada Y . Molecular basis of group A xeroderma pigmentosum: a missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene . Human Genetics . 88 . 6 . 603–7 . Mar 1992 . 1339397 . 10.1007/BF02265282 . 36814493 .
- Satokata I, Tanaka K, Yuba S, Okada Y . Identification of splicing mutations of the last nucleotides of exons, a nonsense mutation, and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum . Mutation Research . 273 . 2 . 203–12 . Mar 1992 . 1372103 . 10.1016/0921-8777(92)90081-d .
- Miyamoto I, Miura N, Niwa H, Miyazaki J, Tanaka K . Mutational analysis of the structure and function of the xeroderma pigmentosum group A complementing protein. Identification of essential domains for nuclear localization and DNA excision repair . The Journal of Biological Chemistry . 267 . 17 . 12182–7 . Jun 1992 . 10.1016/S0021-9258(19)49821-9 . 1601884 . free .
- Satokata I, Tanaka K, Miura N, Miyamoto I, Satoh Y, Kondo S, Okada Y . Characterization of a splicing mutation in group A xeroderma pigmentosum . Proceedings of the National Academy of Sciences of the United States of America . 87 . 24 . 9908–12 . Dec 1990 . 1702221 . 55283 . 10.1073/pnas.87.24.9908 . 1990PNAS...87.9908S . free .
- Miura N, Miyamoto I, Asahina H, Satokata I, Tanaka K, Okada Y . Identification and characterization of xpac protein, the gene product of the human XPAC (xeroderma pigmentosum group A complementing) gene . The Journal of Biological Chemistry . 266 . 29 . 19786–9 . Oct 1991 . 10.1016/S0021-9258(18)55060-2 . 1918083 . free .
- Tanaka K, Miura N, Satokata I, Miyamoto I, Yoshida MC, Satoh Y, Kondo S, Yasui A, Okayama H, Okada Y . Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain . Nature . 348 . 6296 . 73–6 . Nov 1990 . 2234061 . 10.1038/348073a0 . 1990Natur.348...73T . 4346999 .
- Li L, Lu X, Peterson CA, Legerski RJ . An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair . Molecular and Cellular Biology . 15 . 10 . 5396–402 . Oct 1995 . 7565690 . 230789 . 10.1128/mcb.15.10.5396.
- Nagai A, Saijo M, Kuraoka I, Matsuda T, Kodo N, Nakatsu Y, Mimaki T, Mino M, Biggerstaff M, Wood RD . Enhancement of damage-specific DNA binding of XPA by interaction with the ERCC1 DNA repair protein . Biochemical and Biophysical Research Communications . 211 . 3 . 960–6 . Jun 1995 . 7598728 . 10.1006/bbrc.1995.1905 . 1765/60251 . free .
- Farndon PA, Morris DJ, Hardy C, McConville CM, Weissenbach J, Kilpatrick MW, Reis A . Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (Gorlin) syndrome and Fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3 . Genomics . 23 . 2 . 486–9 . Sep 1994 . 7835901 . 10.1006/geno.1994.1528 .
- Park CH, Mu D, Reardon JT, Sancar A . The general transcription-repair factor TFIIH is recruited to the excision repair complex by the XPA protein independent of the TFIIE transcription factor . The Journal of Biological Chemistry . 270 . 9 . 4896–902 . Mar 1995 . 7876263 . 10.1074/jbc.270.9.4896 . free .
- Li L, Elledge SJ, Peterson CA, Bales ES, Legerski RJ . Specific association between the human DNA repair proteins XPA and ERCC1 . Proceedings of the National Academy of Sciences of the United States of America . 91 . 11 . 5012–6 . May 1994 . 8197174 . 43920 . 10.1073/pnas.91.11.5012 . 1994PNAS...91.5012L . free .
- Park CH, Sancar A . Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins . Proceedings of the National Academy of Sciences of the United States of America . 91 . 11 . 5017–21 . May 1994 . 8197175 . 43921 . 10.1073/pnas.91.11.5017 . 1994PNAS...91.5017P . free .
- Satokata I, Iwai K, Matsuda T, Okada Y, Tanaka K . Genomic characterization of the human DNA excision repair-controlling gene XPAC . Gene . 136 . 1–2 . 345–8 . Dec 1993 . 8294029 . 10.1016/0378-1119(93)90493-M .
- Tanaka K . The Japan Society of Human Genetics Award Lecture. Molecular analysis of xeroderma pigmentosum group A gene . The Japanese Journal of Human Genetics . 38 . 1 . 1–14 . Mar 1993 . 8504220 . 10.1007/BF01891230 . free .
- Topping RS, Myrand SP, Williams BL, Albert JC, States JC . Characterization of the human XPA promoter . Gene . 166 . 2 . 341–2 . Dec 1995 . 8543191 . 10.1016/0378-1119(95)00649-4 .
- Lench NJ, Telford EA, Andersen SE, Moynihan TP, Robinson PA, Markham AF . An EST and STS-based YAC contig map of human chromosome 9q22.3 . Genomics . 38 . 2 . 199–205 . Dec 1996 . 8954802 . 10.1006/geno.1996.0616 .
- Selby CP, Sancar A . Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase but is not a helicase and does not disrupt the ternary transcription complex of stalled RNA polymerase II . The Journal of Biological Chemistry . 272 . 3 . 1885–90 . Jan 1997 . 8999876 . 10.1074/jbc.272.3.1885 . free .
- Hayashi T, Takao M, Tanaka K, Yasui A . ERCC1 mutations in UV-sensitive Chinese hamster ovary (CHO) cell lines . Mutation Research . 407 . 3 . 269–76 . Jun 1998 . 9653453 . 10.1016/s0921-8777(98)00013-5 .
External links
Notes and References
- Web site: Entrez Gene: XPA xeroderma pigmentosum, complementation group A.
- Sugitani N, Sivley RM, Perry KE, Capra JA, Chazin WJ . XPA: A key scaffold for human nucleotide excision repair . DNA Repair (Amst.) . 44 . 123–35 . 2016 . 27247238 . 10.1016/j.dnarep.2016.05.018 . 4958585.
- Li L, Elledge SJ, Peterson CA, Bales ES, Legerski RJ . Specific association between the human DNA repair proteins XPA and ERCC1 . Proceedings of the National Academy of Sciences of the United States of America . 91 . 11 . 5012–6 . May 1994 . 8197174 . 43920 . 10.1073/pnas.91.11.5012 . 1994PNAS...91.5012L . free .
- Nagai A, Saijo M, Kuraoka I, Matsuda T, Kodo N, Nakatsu Y, Mimaki T, Mino M, Biggerstaff M, Wood RD . Enhancement of damage-specific DNA binding of XPA by interaction with the ERCC1 DNA repair protein . Biochemical and Biophysical Research Communications . 211 . 3 . 960–6 . Jun 1995 . 7598728 . 10.1006/bbrc.1995.1905 . 1765/60251 . free .
- Li L, Lu X, Peterson CA, Legerski RJ . An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair . Molecular and Cellular Biology . 15 . 10 . 5396–402 . Oct 1995 . 7565690 . 230789 . 10.1128/mcb.15.10.5396.
- Nakatsu Y, Asahina H, Citterio E, Rademakers S, Vermeulen W, Kamiuchi S, Yeo JP, Khaw MC, Saijo M, Kodo N, Matsuda T, Hoeijmakers JH, Tanaka K . XAB2, a novel tetratricopeptide repeat protein involved in transcription-coupled DNA repair and transcription . The Journal of Biological Chemistry . 275 . 45 . 34931–7 . Nov 2000 . 10944529 . 10.1074/jbc.M004936200 . free . 1765/3168 . free .