DNA-(apurinic or apyrimidinic site) endonuclease 2

Definition:

Functions as a weak apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Also displays double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities. Shows robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and is able to remove mismatched nucleotides preferentially. Shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents. In the nucleus functions in the PCNA-dependent BER pathway. Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes. Required for proper cell cycle progression during proliferation of peripheral lymphocytes.

References:

[1]. Tohru Yamamori, et al. SIRT1 deacetylates APE1 and regulates cellular base excision repair. Nucleic Acids Res. 2010 Jan;38(3):832-45. [Content Brief]

[2]. Zusen Fan, et al. Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol. 2003 Feb;4(2):145-53. [Content Brief]

[3]. M M Georgiadis, et al. Evolution of the redox function in mammalian apurinic/apyrimidinic endonuclease. Mutat Res. 2008 Aug 25;643(1-2):54-63. [Content Brief]

[4]. G Fritz, et al. Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox regulation of AP-1. Oncogene. 1999 Jan 28;18(4):1033-40. [Content Brief]

[5]. Junjie U Guo, et al. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011 Apr 29;145(3):423-34. [Content Brief]

[6]. Kai-Ming Chou, et al. An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3' mispaired DNA. Nature. 2002 Feb 7;415(6872):655-9. [Content Brief]

[7]. Y Masuda, et al. Rapid dissociation of human apurinic endonuclease (Ape1) from incised DNA induced by magnesium. J Biol Chem. 1998 Nov 13;273(46):30360-5. [Content Brief]

[8]. Wan-Cheol Kim, et al. Characterization of the endoribonuclease active site of human apurinic/apyrimidinic endonuclease 1. J Mol Biol. 2011 Sep 2;411(5):960-71. [Content Brief]

[9]. Carlo Vascotto, et al. APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Mol Cell Biol. 2009 Apr;29(7):1834-54. [Content Brief]

[10]. D G Rothwell, et al. Asparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1. Nucleic Acids Res. 1996 Nov 1;24(21):4217-21. [Content Brief]

[11]. K Hirota, et al. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8. [Content Brief]

[12]. M M Hsieh, et al. Activation of APE/Ref-1 redox activity is mediated by reactive oxygen species and PKC phosphorylation. Nucleic Acids Res. 2001 Jul 15;29(14):3116-22. [Content Brief]

[13]. U Chung, et al. 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. [Content Brief]

[14]. Peter Burkovics, et al. Human Ape2 protein has a 3'-5' exonuclease activity that acts preferentially on mismatched base pairs. Nucleic Acids Res. 2006 May 10;34(9):2508-15. [Content Brief]

[15]. Ranajoy Chattopadhyay, et al. Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells. Nucleic Acids Res. 2006 Apr 14;34(7):2067-76. [Content Brief]

[16]. R A Bennett, et al. Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7166-9. [Content Brief]

[17]. Tavish Barnes, et al. Identification of Apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA. Nucleic Acids Res. 2009 Jul;37(12):3946-58. [Content Brief]

[18]. Yuming Guo, et al. Granzyme K degrades the redox/DNA repair enzyme Ape1 to trigger oxidative stress of target cells leading to cytotoxicity. Mol Immunol. 2008 Apr;45(8):2225-35. [Content Brief]

[19]. Damiano Fantini, et al. Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions. Nucleic Acids Res. 2010 Dec;38(22):8239-56. [Content Brief]

[20]. David T Kuninger, et al. Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter. Nucleic Acids Res. 2002 Feb 1;30(3):823-9. [Content Brief]

[21]. L J Walker, et al. Identification of residues in the human DNA repair enzyme HAP1 (Ref-1) that are essential for redox regulation of Jun DNA binding. Mol Cell Biol. 1993 Sep;13(9):5370-6. [Content Brief]

[22]. Ranajoy Chattopadhyay, et al. Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1. Mol Cell Biol. 2008 Dec;28(23):7066-80. [Content Brief]

[23]. Peter Burkovics, et al. Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage. Nucleic Acids Res. 2009 Jul;37(13):4247-55. [Content Brief]

[24]. S J Wei, et al. Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. Cancer Res. 2000 Dec 1;60(23):6688-95. [Content Brief]

[25]. Brian R Berquist, et al. Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision. J Mol Biol. 2008 May 23;379(1):17-27. [Content Brief]

[26]. C N Robson, et al. 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 Res. 1991 Oct 25;19(20):5519-23. [Content Brief]

[27]. D Tsuchimoto, et al. Human APE2 protein is mostly localized in the nuclei and to some extent in the mitochondria, while nuclear APE2 is partly associated with proliferating cell nuclear antigen. Nucleic Acids Res. 2001 Jun 1;29(11):2349-60. [Content Brief]

[28]. C V Ramana, et al. Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5061-6. [Content Brief]

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