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APEX1

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

DNA-(apurinic or apyrimidinic site) lyase is an enzyme that in humans is encoded by the APEX1 gene.

Apurinic/apyrimidinic (AP) sites (also called "abasic sites") occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication. All cells, from simple prokaryotes to humans, have evolved systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site, thereby initiating a process known as base excision repair (BER). The APEX gene (alternatively named APE1, HAP1, APEN) encodes the major AP endonuclease in human cells. Splice variants have been found for this gene; all encode the same protein.{{cite web | title = Entrez Gene: APEX1 APEX nuclease (multifunctional DNA repair enzyme) 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=328}}

Interactions

APEX1 has been shown to interact with MUTYH,{{cite journal | vauthors = Parker A, Gu Y, Mahoney W, Lee SH, Singh KK, Lu AL | title = Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair | journal = The Journal of Biological Chemistry | volume = 276 | issue = 8 | pages = 5547–55 | date = February 2001 | pmid = 11092888 | doi = 10.1074/jbc.M008463200 | doi-access = free }} Flap structure-specific endonuclease 1{{cite journal | vauthors = Dianova II, Bohr VA, Dianov GL | title = Interaction of human AP endonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch base excision repair | journal = Biochemistry | volume = 40 | issue = 42 | pages = 12639–44 | date = October 2001 | pmid = 11601988 | doi = 10.1021/bi011117i }} and XRCC1.{{cite journal | vauthors = Vidal AE, Boiteux S, Hickson ID, Radicella JP | title = XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions | journal = The EMBO Journal | volume = 20 | issue = 22 | pages = 6530–9 | date = November 2001 | pmid = 11707423 | pmc = 125722 | doi = 10.1093/emboj/20.22.6530 }}

Aging

Deficiency of APEX1 causes accummulation of DNA damage leading to both cellular senescence and features of premature aging.{{cite journal | vauthors = Li M, Yang X, Lu X, Dai N, Zhang S, Cheng Y, Zhang L, Yang Y, Liu Y, Yang Z, Wang D, Wilson DM | display-authors = 6 | title = APE1 deficiency promotes cellular senescence and premature aging features | journal = Nucleic Acids Research | volume = 46 | issue = 11 | pages = 5664–5677 | date = June 2018 | pmid = 29750271 | pmc = 6009672 | doi = 10.1093/nar/gky326 }} This finding is consistent with the theory that DNA damage is a primary cause of aging.{{cite journal | vauthors = Gensler HL, Bernstein H | title = DNA damage as the primary cause of aging | journal = The Quarterly Review of Biology | volume = 56 | issue = 3 | pages = 279–303 | date = September 1981 | pmid = 7031747 | doi = 10.1086/412317 | s2cid = 20822805 }}

References

{{Reflist}}

Further reading

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  • {{cite journal | vauthors = Mol CD, Hosfield DJ, Tainer JA | title = Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA base excision repair: the 3' ends justify the means | journal = Mutation Research | volume = 460 | issue = 3–4 | pages = 211–29 | date = August 2000 | pmid = 10946230 | doi = 10.1016/s0921-8777(00)00028-8 | doi-access = free }}
  • {{cite journal | vauthors = Fritz G | title = Human APE/Ref-1 protein | journal = The International Journal of Biochemistry & Cell Biology | volume = 32 | issue = 9 | pages = 925–9 | date = September 2000 | pmid = 11084372 | doi = 10.1016/S1357-2725(00)00045-5 }}
  • {{cite journal | vauthors = Fritz G, Grösch S, Tomicic M, Kaina B | title = APE/Ref-1 and the mammalian response to genotoxic stress | journal = Toxicology | volume = 193 | issue = 1–2 | pages = 67–78 | date = November 2003 | pmid = 14599768 | doi = 10.1016/S0300-483X(03)00290-7 }}
  • {{cite journal | vauthors = Tell G, Damante G, Caldwell D, Kelley MR | title = The intracellular localization of APE1/Ref-1: more than a passive phenomenon? | journal = Antioxidants & Redox Signaling | volume = 7 | issue = 3–4 | pages = 367–84 | year = 2005 | pmid = 15706084 | doi = 10.1089/ars.2005.7.367 | hdl = 1805/4802 | hdl-access = free }}
  • {{cite journal | vauthors = Hung RJ, Hall J, Brennan P, Boffetta P | title = Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review | journal = American Journal of Epidemiology | volume = 162 | issue = 10 | pages = 925–42 | date = November 2005 | pmid = 16221808 | doi = 10.1093/aje/kwi318 | doi-access = free }}
  • {{cite journal | vauthors = Dyrkheeva NS, Khodyreva SN, Lavrik OI | title = [Multifunctional human apurinic/apyrimidinic endonuclease 1: the role of additional functions] | journal = Molekuliarnaia Biologiia | volume = 41 | issue = 3 | pages = 450–66 | year = 2007 | pmid = 17685223 }}
  • {{cite journal | vauthors = Harrison L, Ascione G, Menninger JC, Ward DC, Demple B | title = Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12) | journal = Human Molecular Genetics | volume = 1 | issue = 9 | pages = 677–80 | date = December 1992 | pmid = 1284593 | doi = 10.1093/hmg/1.9.677 }}
  • {{cite journal | vauthors = Cheng XB, Bunville J, Patterson TA | title = Nucleotide sequence of a cDNA for an apurinic/apyrimidinic endonuclease from HeLa cells | journal = Nucleic Acids Research | volume = 20 | issue = 2 | pages = 370 | date = January 1992 | pmid = 1371347 | pmc = 310384 | doi = 10.1093/nar/20.2.370 }}
  • {{cite journal | vauthors = Xanthoudakis S, Miao G, Wang F, Pan YC, Curran T | title = Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme | journal = The EMBO Journal | volume = 11 | issue = 9 | pages = 3323–35 | date = September 1992 | pmid = 1380454 | pmc = 556867 | doi = 10.1002/j.1460-2075.1992.tb05411.x}}
  • {{cite journal | vauthors = Zhao B, Grandy DK, Hagerup JM, Magenis RE, Smith L, Chauhan BC, Henner WD | title = The human gene for apurinic/apyrimidinic endonuclease (HAP1): sequence and localization to chromosome 14 band q12 | journal = Nucleic Acids Research | volume = 20 | issue = 15 | pages = 4097–8 | date = August 1992 | pmid = 1380694 | pmc = 334100 | doi = 10.1093/nar/20.15.4097 }}
  • {{cite journal | vauthors = Robson CN, Hochhauser D, Craig R, Rack K, Buckle VJ, Hickson ID | title = Structure of the human DNA repair gene HAP1 and its localisation to chromosome 14q 11.2-12 | journal = Nucleic Acids Research | volume = 20 | issue = 17 | pages = 4417–21 | date = September 1992 | pmid = 1383925 | pmc = 334166 | doi = 10.1093/nar/20.17.4417 }}
  • {{cite journal | vauthors = Seki S, Hatsushika M, Watanabe S, Akiyama K, Nagao K, Tsutsui K | title = cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1131 | issue = 3 | pages = 287–99 | date = July 1992 | pmid = 1627644 | doi = 10.1016/0167-4781(92)90027-w }}
  • {{cite journal | vauthors = Robson CN, Hickson ID | title = Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants | journal = Nucleic Acids Research | volume = 19 | issue = 20 | pages = 5519–23 | date = October 1991 | pmid = 1719477 | pmc = 328951 | doi = 10.1093/nar/19.20.5519 }}
  • {{cite journal | vauthors = Demple B, Herman T, Chen DS | title = Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 24 | pages = 11450–4 | date = December 1991 | pmid = 1722334 | pmc = 53153 | doi = 10.1073/pnas.88.24.11450 | bibcode = 1991PNAS...8811450D | doi-access = free }}
  • {{cite journal | vauthors = Okazaki T, Chung U, Nishishita T, Ebisu S, Usuda S, Mishiro S, Xanthoudakis S, Igarashi T, Ogata E | title = A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium | journal = The Journal of Biological Chemistry | volume = 269 | issue = 45 | pages = 27855–62 | date = November 1994 | doi = 10.1016/S0021-9258(18)46865-2 | pmid = 7961715 | doi-access = free }}
  • {{cite journal | vauthors = Akiyama K, Seki S, Oshida T, Yoshida MC | title = Structure, promoter analysis and chromosomal assignment of the human APEX gene | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1219 | issue = 1 | pages = 15–25 | date = September 1994 | pmid = 8086453 | doi = 10.1016/0167-4781(94)90241-0 }}
  • {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–13 | date = April 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
  • {{cite journal | vauthors = Chung U, Igarashi T, Nishishita T, Iwanari H, Iwamatsu A, Suwa A, Mimori T, Hata K, Ebisu S, Ogata E, Fujita T, Okazaki T | title = The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium | journal = The Journal of Biological Chemistry | volume = 271 | issue = 15 | pages = 8593–8 | date = April 1996 | pmid = 8621488 | doi = 10.1074/jbc.271.15.8593 | doi-access = free }}
  • {{cite journal | vauthors = Rothwell DG, Hickson ID | title = Asparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1 | journal = Nucleic Acids Research | volume = 24 | issue = 21 | pages = 4217–21 | date = November 1996 | pmid = 8932375 | pmc = 146231 | doi = 10.1093/nar/24.21.4217 }}
  • {{cite journal | vauthors = Izumi T, Henner WD, Mitra S | title = Negative regulation of the major human AP-endonuclease, a multifunctional protein | journal = Biochemistry | volume = 35 | issue = 47 | pages = 14679–83 | date = November 1996 | pmid = 8942627 | doi = 10.1021/bi961995u }}

{{Refend}}

External links

  • {{UCSC gene info|APEX1}}

{{PDB Gallery|geneid=328}}

{{Gene-14-stub}}