Apurinic/apyrimidinic (AP) endonuclease is an enzyme that is involved in the DNA base excision repair pathway (BER). Its main role in the repair of damaged or mismatched nucleotides in DNA is to create a nick in the phosphodiester backbone of the AP site created when DNA glycosylase removes the damaged base.
There are four types of AP endonucleases that have been classified according to their mechanism and site of incision. Class I AP endonucleases (EC 4.2.99.18) cleave 3′ to AP sites by a β-lyase mechanism, leaving an unsaturated aldehyde, termed a 3′-(4-hydroxy-5-phospho-2-pentenal) residue, and a 5′-phosphate. Class II AP endonucleases incise DNA 5′ to AP sites by a hydrolytic mechanism, leaving a 3′-hydroxyl and a 5′-deoxyribose phosphate residue.[2] Class III and class IV AP endonucleases also cleave DNA at the phosphate groups 3′ and 5′ to the baseless site, but they generate a 3′-phosphate and a 5′-OH.[3]
Humans have two AP endonucleases, APE1 and APE2. APE1 exhibits robust AP-endonuclease activity, which accounts for >95% of the total cellular activity, and APE1 is considered to be the major AP endonuclease in human cells.[4] Human AP endonuclease (APE1), like most AP endonucleases, is of class II and requires an Mg2+ in its active site in order to carry out its role in base excision repair. The yeast homolog of this enzyme is APN1.[5]
Human AP Endonuclease 2 (APE2), like most AP endonucleases, is also of class II. The exonuclease activity of APE2 is strongly dependent upon metal ions. However, APE2 was more than 5-fold more active in the presence of manganese than of magnesium ions.[4] The conserved domains involved in catalytic activity are located at the N-terminal part of both APE1 and APE2. In addition, the APE2 protein has a C-terminal extension, which is not present in APE1, but can also be found in homologs of human APE2 such as APN2 proteins of S. cerevisiae and S. pombe.[4]
^Clifford D. Mol; Tahide Izumi; Sankar Mitra; John A. Tainer (2000). "DNA-bound structures and mutants reveal abasic DNA binding by APE1 DNA repair and coordination". Nature. 403 (6768): 451–456. doi:10.1038/35000249. PMID 10667800. S2CID 4373743.
^Levin, Joshua D; Demple, Bruce (1990). "Analysis of class II (hydrolytic) and class I (beta-lyase) apurinic/apyrimidinic endonucleases with a synthetic DNA substrate". Nucleic Acids Research. 18 (17): 5069–75. doi:10.1093/nar/18.17.5069. PMC 332125. PMID 1698278.
^Gary M. Myles; Aziz Sancar (1989). "DNA Repair". Chemical Research in Toxicology. 2 (4): 197–226. doi:10.1021/tx00010a001. PMID 2519777.
^ abcBurkovics P, Szukacsov V, Unk I, Haracska L (2006). "Human Ape2 protein has a 3'-5' exonuclease activity that acts preferentially on mismatched base pairs". Nucleic Acids Res. 34 (9): 2508–15. doi:10.1093/nar/gkl259. PMC 1459411. PMID 16687656.
^George W. Teebor; Dina R. Marensein; David M. Wilson III (2004). "Human AP endonuclease (APE1) demonstrates endonucleolytic activity against AP sites in single-stranded DNA". DNA Repair. 3 (5): 527–533. doi:10.1016/j.dnarep.2004.01.010. PMID 15084314.
Apurinic/apyrimidinic (AP) endonuclease is an enzyme that is involved in the DNA base excision repair pathway (BER). Its main role in the repair of damaged...
contain two APendonucleases: endonuclease IV (endoIV) and exonuclease III (exoIII) while in eukaryotes, there is only one APendonuclease. Repair of DNA...
methylated bases, or uracil in DNA. The AP site can then be cleaved by an APendonuclease, leaving 3'-hydroxyl and deoxyribose-5-phosphate termini (see DNA structure)...
specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an APendonuclease. The resulting single-strand break can then be processed...
to identify and repair such sites. Class II APendonucleases cleave the phosphodiester backbone 5' to the AP site, thereby initiating a process known as...
DNA RNase activity 3' phosphatase activity APendonuclease activity (later found to be called endonuclease II). Exonuclease IV adds a water molecule,...
Apurinic/apyrimidinic (AP) sites are a common form of DNA damage that inhibit DNA replication and transcription. APendonuclease 1 (APEX1), an enzyme produced...
methylated cytosine. After an AP site is formed, APendonuclease creates a nick in the phosphodiester backbone of the AP site that was formed when the...
glycosylase, generating an abasic (AP) site. The resulting abasic site is then recognised by enzymes (APendonucleases) that break a phosphodiester bond...
as an intermediary step in base excision repair. These AP sites are removed by APendonucleases, which effect single strand breaks around the site. Nucleotide...
Yang SH, Hazra TK, Mitra S (December 2003). "Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene". The EMBO...
possess AP lyase activity that permits them to cut the phosphodiester bond of DNA, creating a single-strand break without the need for an APendonuclease. β-Elimination...
ExoIII has also been reported to have RNase H, 3´-phosphatase and AP-endonuclease activities. There are many different exonucleases and many are still...
the endonuclease IV consists of several activities such as APendonuclease, 3'-diesterase, 3'->5' exonuclease, and 3'phosphatase. The endonuclease IV is...
deaminase (AID), uracil DNA glycosylase and apyrimidic/apurinic (AP)-endonucleases. AID begins the process of class switching by deaminating (removing...
Bohr VA, Dianov GL (October 2001). "Interaction of human APendonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch...
creating an AP site– a site that lacks a purine or pyrimidine base. In the next step, an APendonuclease creates a nick at the 5' end of the AP site, generating...
experimentally reconstituted using the purified recombinant proteins APendonuclease (mvAPE), uracil-DNA glycosylase (mvUDG), and DNA polymerase X protein...
with human APendonuclease, though interactions between recombinant CSB and E. coli endonuclease IV as well as human N-terminus APendonuclease fragments...
Tomkinson AE, Izumi T, Prasad R, Wilson SH, Mitra S, Hazra TK (2004). "APendonuclease-independent DNA base excision repair in human cells". Mol. Cell. 15...
Endonuclease III-like protein 1 is an enzyme that in humans is encoded by the NTHL1 gene. As reviewed by Li et al., NTHL1 is a bifunctional DNA glycosylase...
Global Information