Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mutat Res Rev Mutat Res
2021 Jan 01;787:108347. doi: 10.1016/j.mrrev.2020.108347.
Show Gene links
Show Anatomy links
Function and molecular mechanisms of APE2 in genome and epigenome integrity.
Lin Y
,
McMahon A
,
Driscoll G
,
Bullock S
,
Zhao J
,
Yan S
.
???displayArticle.abstract???
APE2 is a rising vital player in the maintenance of genome and epigenome integrity. In the past several years, a series of studies have shown the critical roles and functions of APE2. We seek to provide the first comprehensive review on several aspects of APE2 in genome and epigenome integrity. We first summarize the distinct functional domains or motifs within APE2 including EEP (endonuclease/exonuclease/phosphatase) domain, PIP box and Zf-GRF motifs from eight species (i.e., Homo sapiens, Mus musculus, Xenopus laevis, Ciona intestinalis, Arabidopsis thaliana, Schizosaccharomyces pombe, Saccharomyces cerevisiae, and Trypanosoma cruzi). Then we analyze various APE2 nuclease activities and associated DNA substrates, including AP endonuclease, 3'-phosphodiesterase, 3'-phosphatase, and 3'-5' exonuclease activities. We also examine several APE2 interaction proteins, including PCNA, Chk1, APE1, Myh1, and homologous recombination (HR) factors such as Rad51, Rad52, BRCA1, BRCA2, and BARD1. Furthermore, we provide insights into the roles of APE2 in various DNA repair pathways (base excision repair, single-strand break repair, and double-strand break repair), DNA damage response (DDR) pathways (ATR-Chk1 and p53-dependent), immunoglobulin class switch recombination and somatic hypermutation, as well as active DNA demethylation. Lastly, we summarize critical functions of APE2 in growth, development, and diseases. In this review, we provide the first comprehensive perspective which dissects all aspects of the multiple-function protein APE2 in genome and epigenome integrity.
Akbari,
Mitochondrial base excision repair of uracil and AP sites takes place by single-nucleotide insertion and long-patch DNA synthesis.
2008, Pubmed
Akbari,
Mitochondrial base excision repair of uracil and AP sites takes place by single-nucleotide insertion and long-patch DNA synthesis.
2008,
Pubmed
Andres,
Recognition and repair of chemically heterogeneous structures at DNA ends.
2015,
Pubmed
Boiteux,
Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae.
2004,
Pubmed
Brem,
XRCC1 is required for DNA single-strand break repair in human cells.
2005,
Pubmed
Burkovics,
Human Ape2 protein has a 3'-5' exonuclease activity that acts preferentially on mismatched base pairs.
2006,
Pubmed
Burkovics,
Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage.
2009,
Pubmed
Caldecott,
Single-strand break repair and genetic disease.
2008,
Pubmed
Ciccia,
The DNA damage response: making it safe to play with knives.
2010,
Pubmed
Cupello,
Distinct roles of XRCC1 in genome integrity in Xenopus egg extracts.
2019,
Pubmed
,
Xenbase
Cupello,
Cell-free Xenopus egg extracts for studying DNA damage response pathways.
2016,
Pubmed
,
Xenbase
Dan,
Altered gene expression profiles and higher frequency of spontaneous DNA strand breaks in APEX2-null thymus.
2008,
Pubmed
Davis,
Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair.
2014,
Pubmed
Demple,
Exonuclease III and endonuclease IV remove 3' blocks from DNA synthesis primers in H2O2-damaged Escherichia coli.
1986,
Pubmed
Demple,
Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes.
1991,
Pubmed
Eustermann,
Structural Basis of Detection and Signaling of DNA Single-Strand Breaks by Human PARP-1.
2015,
Pubmed
Funakoshi,
CiAPEX2 and CiP0, candidates of AP endonucleases in Ciona intestinalis, have 3'-5' exonuclease activity and contribute to protection against oxidative stress.
2017,
Pubmed
Guikema,
APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination.
2007,
Pubmed
Guikema,
The role of Apex2 in class-switch recombination of immunoglobulin genes.
2010,
Pubmed
Guikema,
Apurinic/apyrimidinic endonuclease 2 is necessary for normal B cell development and recovery of lymphoid progenitors after chemotherapeutic challenge.
2011,
Pubmed
Ha,
A non-canonical role for the DNA glycosylase NEIL3 in suppressing APE1 endonuclease-mediated ssDNA damage.
2020,
Pubmed
,
Xenbase
Hadi,
Second human protein with homology to the Escherichia coli abasic endonuclease exonuclease III.
2000,
Pubmed
Hadi,
Determinants in nuclease specificity of Ape1 and Ape2, human homologues of Escherichia coli exonuclease III.
2002,
Pubmed
Hegde,
Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells.
2008,
Pubmed
Hoitsma,
Structure and function relationships in mammalian DNA polymerases.
2020,
Pubmed
Hossain,
Single-Strand Break End Resection in Genome Integrity: Mechanism and Regulation by APE2.
2018,
Pubmed
Hustedt,
A consensus set of genetic vulnerabilities to ATR inhibition.
2019,
Pubmed
Ide,
Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice.
2004,
Pubmed
Ide,
Characterization of the genomic structure and expression of the mouse Apex2 gene.
2003,
Pubmed
Jackson,
The DNA-damage response in human biology and disease.
2009,
Pubmed
Jensen,
Genomic alterations and abnormal expression of APE2 in multiple cancers.
2020,
Pubmed
Jin,
Interaction of apurinic/apyrimidinic endonuclease 2 (Apn2) with Myh1 DNA glycosylase in fission yeast.
2014,
Pubmed
Johnson,
Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites.
1998,
Pubmed
Johnson,
Yeast DNA 3'-repair diesterase is the major cellular apurinic/apyrimidinic endonuclease: substrate specificity and kinetics.
1988,
Pubmed
Kim,
Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I.
2011,
Pubmed
Kohli,
TET enzymes, TDG and the dynamics of DNA demethylation.
2013,
Pubmed
Krokan,
Base excision repair.
2013,
Pubmed
Kumagai,
Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Kumagai,
Repeated phosphopeptide motifs in Claspin mediate the regulated binding of Chk1.
2003,
Pubmed
,
Xenbase
Kumar,
Role of apurinic/apyrimidinic nucleases in the regulation of homologous recombination in myeloma: mechanisms and translational significance.
2018,
Pubmed
Li,
Human apurinic/apyrimidinic endonuclease 1.
2014,
Pubmed
Li,
APURINIC/APYRIMIDINIC ENDONUCLEASE2 and ZINC FINGER DNA 3'-PHOSPHOESTERASE Play Overlapping Roles in the Maintenance of Epigenome and Genome Stability.
2018,
Pubmed
Li,
Apn2 resolves blocked 3' ends and suppresses Top1-induced mutagenesis at genomic rNMP sites.
2019,
Pubmed
Li,
An AP endonuclease functions in active DNA demethylation and gene imprinting in Arabidopsis [corrected].
2015,
Pubmed
Lin,
APE2 promotes DNA damage response pathway from a single-strand break.
2018,
Pubmed
,
Xenbase
Lin,
APE1 senses DNA single-strand breaks for repair and signaling.
2020,
Pubmed
,
Xenbase
Lin,
Methods for Studying DNA Single-Strand Break Repair and Signaling in Xenopus laevis Egg Extracts.
2019,
Pubmed
,
Xenbase
Lindahl,
Instability and decay of the primary structure of DNA.
1993,
Pubmed
Mailand,
Regulation of PCNA-protein interactions for genome stability.
2013,
Pubmed
Malyarchuk,
DNA repair of clustered lesions in mammalian cells: involvement of non-homologous end-joining.
2008,
Pubmed
Masani,
Apurinic/apyrimidinic endonuclease 1 is the essential nuclease during immunoglobulin class switch recombination.
2013,
Pubmed
Mengwasser,
Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets.
2019,
Pubmed
Metintas,
Environmental asbestos exposure and malignant pleural mesothelioma.
1999,
Pubmed
Mol,
Abasic site recognition by two apurinic/apyrimidinic endonuclease families in DNA base excision repair: the 3' ends justify the means.
2000,
Pubmed
Murphy,
Requirement for abasic endonuclease gene homologues in Arabidopsis seed development.
2009,
Pubmed
Nakabeppu,
Biological significance of the defense mechanisms against oxidative damage in nucleic acids caused by reactive oxygen species: from mitochondria to nuclei.
2004,
Pubmed
Petrucelli,
Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2.
2010,
Pubmed
Ribar,
The major role of human AP-endonuclease homolog Apn2 in repair of abasic sites in Schizosaccharomyces pombe.
2004,
Pubmed
Robson,
Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants.
1991,
Pubmed
Sabouri,
Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes.
2009,
Pubmed
Schrader,
The roles of APE1, APE2, DNA polymerase beta and mismatch repair in creating S region DNA breaks during antibody class switch.
2009,
Pubmed
Sekiguchi,
Site-specific ribonuclease activity of eukaryotic DNA topoisomerase I.
1997,
Pubmed
Sepúlveda,
Expression, functionality, and localization of apurinic/apyrimidinic endonucleases in replicative and non-replicative forms of Trypanosoma cruzi.
2014,
Pubmed
Stavnezer,
Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation.
2014,
Pubmed
Stratigopoulou,
Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences.
2020,
Pubmed
Sugimoto,
Roles of base excision repair enzymes Nth1p and Apn2p from Schizosaccharomyces pombe in processing alkylation and oxidative DNA damage.
2005,
Pubmed
Svilar,
Base excision repair and lesion-dependent subpathways for repair of oxidative DNA damage.
2011,
Pubmed
Tell,
The many functions of APE1/Ref-1: not only a DNA repair enzyme.
2009,
Pubmed
Thompson,
New insights into abasic site repair and tolerance.
2020,
Pubmed
Tsuchimoto,
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.
2001,
Pubmed
Unk,
3'-phosphodiesterase and 3'-->5' exonuclease activities of yeast Apn2 protein and requirement of these activities for repair of oxidative DNA damage.
2001,
Pubmed
Unk,
Apurinic endonuclease activity of yeast Apn2 protein.
2000,
Pubmed
Unk,
Stimulation of 3'-->5' exonuclease and 3'-phosphodiesterase activities of yeast apn2 by proliferating cell nuclear antigen.
2002,
Pubmed
Wallace,
APE2 Zf-GRF facilitates 3'-5' resection of DNA damage following oxidative stress.
2017,
Pubmed
,
Xenbase
Wang,
Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.
2011,
Pubmed
Willis,
APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress.
2013,
Pubmed
,
Xenbase
Wilson,
Incision activity of human apurinic endonuclease (Ape) at abasic site analogs in DNA.
1995,
Pubmed
Wu,
TRAIP is a master regulator of DNA interstrand crosslink repair.
2019,
Pubmed
,
Xenbase
Xanthoudakis,
Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity.
1992,
Pubmed
Xanthoudakis,
The redox/DNA repair protein, Ref-1, is essential for early embryonic development in mice.
1996,
Pubmed
Yan,
Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress.
2014,
Pubmed
Yan,
Resolution of a complex crisis at DNA 3' termini.
2019,
Pubmed
Yui,
The DNA repair enzyme apurinic/apyrimidinic endonuclease (Apex nuclease) 2 has the potential to protect against down-regulation of chondrocyte activity in osteoarthritis.
2014,
Pubmed
Zheng,
Identification of APEX2 as an oncogene in liver cancer.
2020,
Pubmed
Zhu,
Active DNA demethylation mediated by DNA glycosylases.
2009,
Pubmed
Álvarez-Quilón,
Endogenous DNA 3' Blocks Are Vulnerabilities for BRCA1 and BRCA2 Deficiency and Are Reversed by the APE2 Nuclease.
2020,
Pubmed
Ömeroğlu Şimşek,
Evaluation of gene expression levels in the diagnosis of lung adenocarcinoma and malignant pleural mesothelioma.
2020,
Pubmed
