DNA-(apurinic or apyrimidinic site) lyase is an enzyme that in humans is encoded by the APEX1gene.
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.[5]
Deficiency of APEX1 causes accummulation of DNA damage leading to both cellular senescence and features of premature aging.[9] This finding is consistent with the theory that DNA damage is a primary cause of aging.[10]
^Dianova II, Bohr VA, Dianov GL (October 2001). "Interaction of human AP endonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch base excision repair". Biochemistry. 40 (42): 12639–44. doi:10.1021/bi011117i. PMID11601988.
^Gensler HL, Bernstein H (September 1981). "DNA damage as the primary cause of aging". The Quarterly Review of Biology. 56 (3): 279–303. doi:10.1086/412317. PMID7031747. S2CID20822805.
Fritz G, Grösch S, Tomicic M, Kaina B (November 2003). "APE/Ref-1 and the mammalian response to genotoxic stress". Toxicology. 193 (1–2): 67–78. doi:10.1016/S0300-483X(03)00290-7. PMID14599768.
Tell G, Damante G, Caldwell D, Kelley MR (2005). "The intracellular localization of APE1/Ref-1: more than a passive phenomenon?". Antioxidants & Redox Signaling. 7 (3–4): 367–84. doi:10.1089/ars.2005.7.367. hdl:1805/4802. PMID15706084.
Dyrkheeva NS, Khodyreva SN, Lavrik OI (2007). "[Multifunctional human apurinic/apyrimidinic endonuclease 1: the role of additional functions]". Molekuliarnaia Biologiia. 41 (3): 450–66. PMID17685223.
Harrison L, Ascione G, Menninger JC, Ward DC, Demple B (December 1992). "Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12)". Human Molecular Genetics. 1 (9): 677–80. doi:10.1093/hmg/1.9.677. PMID1284593.
Akiyama K, Seki S, Oshida T, Yoshida MC (September 1994). "Structure, promoter analysis and chromosomal assignment of the human APEX gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1219 (1): 15–25. doi:10.1016/0167-4781(94)90241-0. PMID8086453.
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID8619474.
Izumi T, Henner WD, Mitra S (November 1996). "Negative regulation of the major human AP-endonuclease, a multifunctional protein". Biochemistry. 35 (47): 14679–83. doi:10.1021/bi961995u. PMID8942627.
1bix: THE CRYSTAL STRUCTURE OF THE HUMAN DNA REPAIR ENDONUCLEASE HAP1 SUGGESTS THE RECOGNITION OF EXTRA-HELICAL DEOXYRIBOSE AT DNA ABASIC SITES
1de8: HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE-1 (APE1) BOUND TO ABASIC DNA
1de9: HUMAN APE1 ENDONUCLEASE WITH BOUND ABASIC DNA AND MN2+ ION
1dew: CRYSTAL STRUCTURE OF HUMAN APE1 BOUND TO ABASIC DNA
1e9n: A SECOND DIVALENT METAL ION IN THE ACTIVE SITE OF A NEW CRYSTAL FORM OF HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE, APE1, AND ITS IMPLICATIONS FOR THE CATALYTIC MECHANISM
1hd7: A SECOND DIVALENT METAL ION IN THE ACTIVE SITE OF A NEW CRYSTAL FORM OF HUMAN APURINIC/APYRIDINIMIC ENDONUCLEASE, APE1, AND ITS IMPLICATIONS FOR THE CATALYTIC MECHANISM
2isi: Crystal structure of Ape1 from Homo sapiens in a new crystal form complexed with a ligand
