APN1/YKL114C Summary Help

Standard Name APN1 1
Systematic Name YKL114C
Feature Type ORF, Verified
Description Major apurinic/apyrimidinic endonuclease; 3'-repair diesterase; involved in repair of DNA damage by oxidation and alkylating agents; also functions as a 3'-5' exonuclease to repair 7,8-dihydro-8-oxodeoxyguanosine; genetically interacts with NTG1 to maintain mitochondrial genome integrity (1, 2, 3, 4 and see Summary Paragraph)
Name Description APurinic/apyrimidinic eNdonuclease 1
Chromosomal Location
ChrXI:224455 to 223352 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All APN1 GO evidence and references
  View Computational GO annotations for APN1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Classical genetics
null
Large-scale survey
null
unspecified
Resources
175 total interaction(s) for 82 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 9
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 2
  • Biochemical Activity: 3
  • Reconstituted Complex: 2
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 2
  • Negative Genetic: 18
  • Phenotypic Enhancement: 41
  • Phenotypic Suppression: 14
  • Positive Genetic: 2
  • Synthetic Growth Defect: 33
  • Synthetic Lethality: 29
  • Synthetic Rescue: 16

Resources
Expression Summary
histogram
Resources
Length (a.a.) 367
Molecular Weight (Da) 41,439
Isoelectric Point (pI) 8.33
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXI:224455 to 223352 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1104 224455..223352 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001597
SUMMARY PARAGRAPH for APN1

APN1 and APN2 encode multi-functional enzymes involved in the repair of damaged bases in DNA (reviewed in 5 and 6). Both Apn1p and Apn2p possess an apurinic/apyrimidinic (AP) endonuclease activity, a 3'-diesterase activity, and a 3' to 5' exonuclease activity (1, 7, 8). However, Apn1p constitutes the major apurinic/apyrimidinic (AP) endonuclease and 3'-phosphodiesterase in vivo, constituting close to 97% of these activities (1). During base excision repair (BER), the AP-endonuclease activity nicks the 5' side of abasic sites that are generated by the removal of oxidized and alkylated bases. This creates a single-strand break that contains a 3' hydroxyl group in preparation for DNA synthesis (9, 8). The 3'-phosphodiesterase activity is able to remove a wide range of 3' moieties at end of single-strand breaks in order to generate a 3' hydroxyl group (10, 7). The 3' to 5' exonuclease activity removes single nucleotides at a nick, such as 8oxodGMP that is mispaired with adenine/cytosine, leaving a single-nucleotide gap (3, 11, 7).

Apn1p has functions not shared with Apn2p. Apn1p also catalyzes the cleavage of a tyrosyl-DNA phosphodiester bond, suggesting that it could have a role in the removal of topoisomerase I covalently bound to DNA in an alternate pathway to that mediated by Tdp1p (12). In addition, Apn1p is involved in the repair of mitochondrial DNA. apn1 mutant strains are sensitive to DNA damaging agents such as methyl-methane sulfonate (MMS) and hydrogen peroxide (13, 2, 14), have an increase in single base pair mutations in the nuclear and mitochondrial genome (15, 14), and are extremely sensitive to thymidine deprivation (16).

Apn1p has sequence similarity to E. coli endonuclease IV (1). Homologs have also been identified in S. pombe and C. elegans (17, 18, 19).

Last updated: 2006-10-26 Contact SGD

References cited on this page View Complete Literature Guide for APN1
1) Popoff SC, et al.  (1990) Yeast structural gene (APN1) for the major apurinic endonuclease: homology to Escherichia coli endonuclease IV. Proc Natl Acad Sci U S A 87(11):4193-7
2) Ramotar D, et al.  (1991) Cellular role of yeast Apn1 apurinic endonuclease/3'-diesterase: repair of oxidative and alkylation DNA damage and control of spontaneous mutation. Mol Cell Biol 11(9):4537-44
3) Ishchenko AA, et al.  (2005) The 3'->5' exonuclease of Apn1 provides an alternative pathway to repair 7,8-dihydro-8-oxodeoxyguanosine in Saccharomyces cerevisiae. Mol Cell Biol 25(15):6380-90
4) Phadnis N, et al.  (2006) Ntg1p, the base excision repair protein, generates mutagenic intermediates in yeast mitochondrial DNA. DNA Repair (Amst) 5(7):829-39
5) Boiteux S and Guillet M  (2004) Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisiae. DNA Repair (Amst) 3(1):1-12
6) Ramotar D  (1997) The apurinic-apyrimidinic endonuclease IV family of DNA repair enzymes. Biochem Cell Biol 75(4):327-36
7) Unk I, et al.  (2001) 3'-phosphodiesterase and 3'-->5' exonuclease activities of yeast Apn2 protein and requirement of these activities for repair of oxidative DNA damage. Mol Cell Biol 21(5):1656-61
8) Unk I, et al.  (2000) Apurinic endonuclease activity of yeast Apn2 protein. J Biol Chem 275(29):22427-34
9) Johnson AW and Demple B  (1988) Yeast DNA 3'-repair diesterase is the major cellular apurinic/apyrimidinic endonuclease: substrate specificity and kinetics. J Biol Chem 263(34):18017-22
10) Johnson AW and Demple B  (1988) Yeast DNA diesterase for 3'-fragments of deoxyribose: purification and physical properties of a repair enzyme for oxidative DNA damage. J Biol Chem 263(34):18009-16
11) Vance JR and Wilson TE  (2001) Repair of DNA strand breaks by the overlapping functions of lesion-specific and non-lesion-specific DNA 3' phosphatases. Mol Cell Biol 21(21):7191-8
12) Liu C, et al.  (2002) Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1. Proc Natl Acad Sci U S A 99(23):14970-5
13) Hanna M, et al.  (2004) Involvement of two endonuclease III homologs in the base excision repair pathway for the processing of DNA alkylation damage in Saccharomyces cerevisiae. DNA Repair (Amst) 3(1):51-9
14) Vongsamphanh R, et al.  (2001) Pir1p mediates translocation of the yeast Apn1p endonuclease into the mitochondria to maintain genomic stability. Mol Cell Biol 21(5):1647-55
15) Kunz BA, et al.  (1994) Specificity of the mutator caused by deletion of the yeast structural gene (APN1) for the major apurinic endonuclease. Proc Natl Acad Sci U S A 91(17):8165-9
16) Dornfeld K and Johnson M  (2005) AP endonuclease deficiency results in extreme sensitivity to thymidine deprivation. Nucleic Acids Res 33(20):6644-53
17) Ramotar D, et al.  (1998) Schizosaccharomyces pombe apn1 encodes a homologue of the Escherichia coli endonuclease IV family of DNA repair proteins. Biochim Biophys Acta 1396(1):15-20
18) Masson JY, et al.  (1996) The Caenorhabditis elegans gene CeAPN1 encodes a homolog of Escherichia coli and yeast apurinic/apyrimidinic endonuclease. Gene 179(2):291-3
19) Shatilla A, et al.  (2005) Identification of two apurinic/apyrimidinic endonucleases from Caenorhabditis elegans by cross-species complementation. DNA Repair (Amst) 4(6):655-70