Biology:APEX1

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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 APEX1 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.

Interactions

APEX1 has been shown to interact with MUTYH, Flap structure-specific endonuclease 1 and XRCC1.

Aging

Deficiency of APEX1 causes accummulation of DNA damage leading to both cellular senescence and features of premature aging. This finding is consistent with the theory that DNA damage is a primary cause of aging.

Further reading

• "Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA base excision repair: the 3' ends justify the means". Mutation Research 460 (3–4): 211–29. August 2000. doi:10.1016/s0921-8777(00)00028-8. PMID 10946230. 
• "Human APE/Ref-1 protein". The International Journal of Biochemistry & Cell Biology 32 (9): 925–9. September 2000. doi:10.1016/S1357-2725(00)00045-5. PMID 11084372. 
• "APE/Ref-1 and the mammalian response to genotoxic stress". Toxicology 193 (1–2): 67–78. November 2003. doi:10.1016/S0300-483X(03)00290-7. PMID 14599768. 
• "The intracellular localization of APE1/Ref-1: more than a passive phenomenon?". Antioxidants & Redox Signaling 7 (3–4): 367–84. 2005. doi:10.1089/ars.2005.7.367. PMID 15706084. 
• "Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review". American Journal of Epidemiology 162 (10): 925–42. November 2005. doi:10.1093/aje/kwi318. PMID 16221808. 
• "[Multifunctional human apurinic/apyrimidinic endonuclease 1: the role of additional functions]". Molekuliarnaia Biologiia 41 (3): 450–66. 2007. PMID 17685223. 
• "Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12)". Human Molecular Genetics 1 (9): 677–80. December 1992. doi:10.1093/hmg/1.9.677. PMID 1284593. 
• "Nucleotide sequence of a cDNA for an apurinic/apyrimidinic endonuclease from HeLa cells". Nucleic Acids Research 20 (2): 370. January 1992. doi:10.1093/nar/20.2.370. PMID 1371347. 
• "Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme". The EMBO Journal 11 (9): 3323–35. September 1992. doi:10.1002/j.1460-2075.1992.tb05411.x. PMID 1380454. 
• "The human gene for apurinic/apyrimidinic endonuclease (HAP1): sequence and localization to chromosome 14 band q12". Nucleic Acids Research 20 (15): 4097–8. August 1992. doi:10.1093/nar/20.15.4097. PMID 1380694. 
• "Structure of the human DNA repair gene HAP1 and its localisation to chromosome 14q 11.2-12". Nucleic Acids Research 20 (17): 4417–21. September 1992. doi:10.1093/nar/20.17.4417. PMID 1383925. 
• "cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1131 (3): 287–99. July 1992. doi:10.1016/0167-4781(92)90027-w. PMID 1627644. 
• "Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants". Nucleic Acids Research 19 (20): 5519–23. October 1991. doi:10.1093/nar/19.20.5519. PMID 1719477. 
• "Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes". Proceedings of the National Academy of Sciences of the United States of America 88 (24): 11450–4. December 1991. doi:10.1073/pnas.88.24.11450. PMID 1722334. Bibcode: 1991PNAS...8811450D. 
• "A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium". The Journal of Biological Chemistry 269 (45): 27855–62. November 1994. doi:10.1016/S0021-9258(18)46865-2. PMID 7961715. 
• "Structure, promoter analysis and chromosomal assignment of the human APEX gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1219 (1): 15–25. September 1994. doi:10.1016/0167-4781(94)90241-0. PMID 8086453. 
• "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry 236 (1): 107–13. April 1996. doi:10.1006/abio.1996.0138. PMID 8619474. 
• "The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium". The Journal of Biological Chemistry 271 (15): 8593–8. April 1996. doi:10.1074/jbc.271.15.8593. PMID 8621488. 
• "Asparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1". Nucleic Acids Research 24 (21): 4217–21. November 1996. doi:10.1093/nar/24.21.4217. PMID 8932375. 
• "Negative regulation of the major human AP-endonuclease, a multifunctional protein". Biochemistry 35 (47): 14679–83. November 1996. doi:10.1021/bi961995u. PMID 8942627. 

External links

• Human APEX1 genome location and APEX1 gene details page in the UCSC Genome Browser.