APN1

Summary

Gene Symbol: APN1
Description: DNA-(apurinic or apyrimidinic site) lyase APN1
Alias: DNA-(apurinic or apyrimidinic site) lyase APN1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Hanna M, Chow B, Morey N, Jinks Robertson S, Doetsch P, Xiao W. 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). 2004;3:51-9 pubmed
    ..We previously reported that yeast cells deficient in the two AP endonucleases (apn1 apn2 double mutant) are extremely sensitive to killing by a model DNA alkylating agent methyl methanesulfonate (MMS)..
  2. Guillet M, Boiteux S. Endogenous DNA abasic sites cause cell death in the absence of Apn1, Apn2 and Rad1/Rad10 in Saccharomyces cerevisiae. EMBO J. 2002;21:2833-41 pubmed
    In Saccharomyces cerevisiae, mutations in APN1, APN2 and either RAD1 or RAD10 genes are synthetic lethal. In fact, apn1 apn2 rad1 triple mutants can form microcolonies of approximately 300 cells...
  3. Wang Z, Wu X, Friedberg E. Molecular mechanism of base excision repair of uracil-containing DNA in yeast cell-free extracts. J Biol Chem. 1997;272:24064-71 pubmed
    ..Using uracil-containing DNA as a model substrate, we demonstrate that yeast BER requires Apn1 protein, an Escherichia coli endonuclease IV homolog...
  4. Torres Ramos C, Johnson R, Prakash L, Prakash S. Evidence for the involvement of nucleotide excision repair in the removal of abasic sites in yeast. Mol Cell Biol. 2000;20:3522-8 pubmed
    ..In Saccharomyces cerevisiae, AP sites are removed via the action of two class II AP endonucleases, Apn1 and Apn2...
  5. Wu X, Wang Z. Relationships between yeast Rad27 and Apn1 in response to apurinic/apyrimidinic (AP) sites in DNA. Nucleic Acids Res. 1999;27:956-62 pubmed
    Yeast Rad27 is a 5'-->3' exonuclease and a flap endo-nuclease. Apn1 is the major apurinic/apyrimidinic (AP) endonuclease in yeast. The rad27 deletion mutants are highly sensitive to methylmethane sulfonate (MMS)...
  6. Guillet M, Boiteux S. Origin of endogenous DNA abasic sites in Saccharomyces cerevisiae. Mol Cell Biol. 2003;23:8386-94 pubmed
    ..In Saccharomyces cerevisiae, an apn1 apn2 rad1 triple mutant is inviable because of its incapacity to repair AP sites and related 3'-blocked single-..
  7. Ma W, Resnick M, Gordenin D. Apn1 and Apn2 endonucleases prevent accumulation of repair-associated DNA breaks in budding yeast as revealed by direct chromosomal analysis. Nucleic Acids Res. 2008;36:1836-46 pubmed publisher
    ..This approach provided direct physical evidence that Apn1 and Apn2 not only repair cellular base damage but also prevent break accumulation that can result from AP sites ..
  8. Johnson R, Torres Ramos C, Izumi T, Mitra S, Prakash S, Prakash L. Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites. Genes Dev. 1998;12:3137-43 pubmed
    Abasic (AP) sites arise in DNA through spontaneous base loss and enzymatic removal of damaged bases. APN1 encodes the major AP-endonuclease of Saccharomyces cerevisiae...
  9. Swanson R, Morey N, Doetsch P, Jinks Robertson S. Overlapping specificities of base excision repair, nucleotide excision repair, recombination, and translesion synthesis pathways for DNA base damage in Saccharomyces cerevisiae. Mol Cell Biol. 1999;19:2929-35 pubmed
    ..The additional disruption of the RAD52 gene in the ntg1 ntg2 apn1 triple mutant confers a high degree of sensitivity to these agents...

More Information

Publications58

  1. Xiao W, Chow B, Hanna M, Doetsch P. Deletion of the MAG1 DNA glycosylase gene suppresses alkylation-induced killing and mutagenesis in yeast cells lacking AP endonucleases. Mutat Res. 2001;487:137-47 pubmed
    ..We found that yeast cells deficient in the two AP endonucleases (apn1 apn2 double mutant) are extremely sensitive to killing by methyl methanesulfonate (MMS), a model DNA alkylating ..
  2. Vongsamphanh R, Fortier P, Ramotar D. Pir1p mediates translocation of the yeast Apn1p endonuclease into the mitochondria to maintain genomic stability. Mol Cell Biol. 2001;21:1647-55 pubmed
    ..Yeast Apn1p is localized to the nucleus, where it functions to cleave abasic sites, and apn1 Delta mutants are hypersensitive to agents such as methyl methanesulfonate (MMS) that induce abasic sites...
  3. Karumbati A, Deshpande R, Jilani A, Vance J, Ramotar D, Wilson T. The role of yeast DNA 3'-phosphatase Tpp1 and rad1/Rad10 endonuclease in processing spontaneous and induced base lesions. J Biol Chem. 2003;278:31434-43 pubmed
    ..Fpg conferred Tpp1-dependent resistance to methylmethane sulfonate in yeast lacking the abasic endonucleases Apn1 and Apn2...
  4. Popoff S, Spira A, Johnson A, Demple B. Yeast structural gene (APN1) for the major apurinic endonuclease: homology to Escherichia coli endonuclease IV. Proc Natl Acad Sci U S A. 1990;87:4193-7 pubmed
    ..We have cloned the yeast structural gene (APN1) encoding this AP endonuclease/3'-repair diesterase by immunological screening of a yeast genomic DNA expression ..
  5. Guillet M, van der Kemp P, Boiteux S. dUTPase activity is critical to maintain genetic stability in Saccharomyces cerevisiae. Nucleic Acids Res. 2006;34:2056-66 pubmed
    ..Therefore, the normal cellular metabolism, and not only its byproducts, is an important source of endogenous DNA damage and genetic instability in eukaryotic cells. ..
  6. Karumbati A, Wilson T. Abrogation of the Chk1-Pds1 checkpoint leads to tolerance of persistent single-strand breaks in Saccharomyces cerevisiae. Genetics. 2005;169:1833-44 pubmed
    In budding yeast, Apn1, Apn2, Tpp1, and Rad1/Rad10 are important enzymes in the removal of spontaneous DNA lesions. apn1 apn2 rad1 yeast are inviable due to accumulation of abasic sites and strand breaks with 3' blocking lesions...
  7. Bennett R. The Saccharomyces cerevisiae ETH1 gene, an inducible homolog of exonuclease III that provides resistance to DNA-damaging agents and limits spontaneous mutagenesis. Mol Cell Biol. 1999;19:1800-9 pubmed
    ..reading frame were made in a wild-type strain and a strain deficient in the known yeast AP endonuclease encoded by APN1. eth1 strains were not more sensitive to killing by MMS, hydrogen peroxide, or phleomycin D1, whereas apn1 strains ..
  8. Guzder S, Torres Ramos C, Johnson R, Haracska L, Prakash L, Prakash S. Requirement of yeast Rad1-Rad10 nuclease for the removal of 3'-blocked termini from DNA strand breaks induced by reactive oxygen species. Genes Dev. 2004;18:2283-91 pubmed
    ..studies indicate that 3'-blocked termini are removed in yeast by the three competing pathways that involve the Apn1, Apn2, and Rad1-Rad10 nucleases, and we show that the Rad1-Rad10 nuclease proficiently cleaves DNA modified with a ..
  9. Xiao W, Chow B. Synergism between yeast nucleotide and base excision repair pathways in the protection against DNA methylation damage. Curr Genet. 1998;33:92-9 pubmed
    ..pathway is initiated by a Mag1 3-methyladenine DNA glycosylase that removes the damaged base, followed by the Apn1 apurinic/apyrimidinic endonuclease which cleaves the DNA strand at the abasic site for subsequent repair and ..
  10. Collura A, Kemp P, Boiteux S. Abasic sites linked to dUTP incorporation in DNA are a major cause of spontaneous mutations in absence of base excision repair and Rad17-Mec3-Ddc1 (9-1-1) DNA damage checkpoint clamp in Saccharomyces cerevisiae. DNA Repair (Amst). 2012;11:294-303 pubmed publisher
    ..The results show that mec1 sml1, rad53 sml1 and rad9 is synthetic lethal with apn1 apn2...
  11. Kim N, Jinks Robertson S. dUTP incorporation into genomic DNA is linked to transcription in yeast. Nature. 2009;459:1150-3 pubmed publisher
    ..These results show an unexpected relationship between transcription and the fidelity of DNA synthesis, and raise intriguing cell biological issues with regard to nucleotide pool compartmentalization. ..
  12. Godin S, Zhang Z, Herken B, Westmoreland J, Lee A, Mihalevic M, et al. The Shu complex promotes error-free tolerance of alkylation-induced base excision repair products. Nucleic Acids Res. 2016;44:8199-215 pubmed publisher
    ..Together, our work demonstrates that the Shu complex's promotion of Rad51 pre-synaptic filaments is critical for high-fidelity bypass of multiple replication-blocking lesion. ..
  13. Ishchenko A, Yang X, Ramotar D, Saparbaev M. The 3'->5' exonuclease of Apn1 provides an alternative pathway to repair 7,8-dihydro-8-oxodeoxyguanosine in Saccharomyces cerevisiae. Mol Cell Biol. 2005;25:6380-90 pubmed
    ..cerevisiae AP endonuclease Apn1, which is endowed with a robust progressive 3'-->5' exonuclease activity towards duplex DNA...
  14. Matuo R, Sousa F, Escargueil A, Soares D, Grivicich I, Saffi J, et al. DNA repair pathways involved in repair of lesions induced by 5-fluorouracil and its active metabolite FdUMP. Biochem Pharmacol. 2010;79:147-53 pubmed publisher
    ..The results revealed an important role of BER, since BER-mutants (ntg1, ntg2, apn1, apn2) showed pronounced sensitivity to both 5-FU and FdUMP...
  15. Ragu S, Faye G, Iraqui I, Masurel Heneman A, Kolodner R, Huang M. Oxygen metabolism and reactive oxygen species cause chromosomal rearrangements and cell death. Proc Natl Acad Sci U S A. 2007;104:9747-52 pubmed
    ..H(2)O(2) treatment also induced the GCRs. Our results provide in vivo evidence that oxygen metabolism and reactive oxygen species are important sources of DNA damages that can lead to GCRs and lethal effects in S. cerevisiae. ..
  16. Phadnis N, Mehta R, Meednu N, Sia E. Ntg1p, the base excision repair protein, generates mutagenic intermediates in yeast mitochondrial DNA. DNA Repair (Amst). 2006;5:829-39 pubmed
    ..In addition, loss of Apn1p also suppressed mitochondrial point mutations. Our work suggests that both Ntg1p and Apn1p generate mutagenic intermediates in the yeast mitochondrial genome. ..
  17. Hoopes J, Hughes A, Hobson L, Cortez L, Brown A, Roberts S. Avoidance of APOBEC3B-induced mutation by error-free lesion bypass. Nucleic Acids Res. 2017;45:5243-5254 pubmed publisher
    ..Strains lacking Apn1, Apn2, Ntg1, Ntg2 or Rev3 displayed wild-type frequencies of APOBEC3B-induced canavanine resistance (CanR)...
  18. Dyakonova E, Koval V, Lomzov A, Ishchenko A, Fedorova O. The role of His-83 of yeast apurinic/apyrimidinic endonuclease Apn1 in catalytic incision of abasic sites in DNA. Biochim Biophys Acta. 2015;1850:1297-309 pubmed publisher
    The apurinic/apyrimidinic (AP) endonuclease Apn1 from Saccharomyces cerevisiae is a key enzyme involved in the base excision repair (BER) at the cleavage stage of abasic sites (AP sites) in DNA. The crystal structure of Apn1 from S...
  19. Vance J, Wilson T. Repair of DNA strand breaks by the overlapping functions of lesion-specific and non-lesion-specific DNA 3' phosphatases. Mol Cell Biol. 2001;21:7191-8 pubmed
    In Saccharomyces cerevisiae, the apurinic/apyrimidinic (AP) endonucleases Apn1 and Apn2 act as alternative pathways for the removal of various 3'-terminal blocking lesions from DNA strand breaks and in the repair of abasic sites, which ..
  20. Kim N, Jinks Robertson S. Abasic sites in the transcribed strand of yeast DNA are removed by transcription-coupled nucleotide excision repair. Mol Cell Biol. 2010;30:3206-15 pubmed publisher
    ..Such transcription-coupled NER of AP sites may explain previously suggested links between the BER pathway and transcription. ..
  21. Conde F, San Segundo P. Role of Dot1 in the response to alkylating DNA damage in Saccharomyces cerevisiae: regulation of DNA damage tolerance by the error-prone polymerases Polzeta/Rev1. Genetics. 2008;179:1197-210 pubmed publisher
    ..or totally suppresses the MMS sensitivity of various DNA repair mutants (rad52, rad54, yku80, rad1, rad14, apn1, rad5, rad30)...
  22. Doerfler L, Schmidt K. Exo1 phosphorylation status controls the hydroxyurea sensitivity of cells lacking the Pol32 subunit of DNA polymerases delta and zeta. DNA Repair (Amst). 2014;24:26-36 pubmed publisher
  23. Kelberg E, Kovaltsova S, Alekseev S, Fedorova I, Gracheva L, Evstukhina T, et al. HIM1, a new yeast Saccharomyces cerevisiae gene playing a role in control of spontaneous and induced mutagenesis. Mutat Res. 2005;578:64-78 pubmed
    ..We tested the induced mutagenesis in double mutants carrying him1 mutation and mutations in other repair genes: apn1, blocking base excision repair; rad2, rev3, and rad54, blocking three principal DNA repair pathways; pms1, blocking ..
  24. Mániková D, Vlasáková D, Loduhová J, Letavayová L, Vigasová D, Krascsenitsová E, et al. Investigations on the role of base excision repair and non-homologous end-joining pathways in sodium selenite-induced toxicity and mutagenicity in Saccharomyces cerevisiae. Mutagenesis. 2010;25:155-62 pubmed publisher
  25. Wurtele H, Kaiser G, Bacal J, St Hilaire E, Lee E, Tsao S, et al. Histone H3 lysine 56 acetylation and the response to DNA replication fork damage. Mol Cell Biol. 2012;32:154-72 pubmed publisher
  26. Pawar V, Jingjing L, Patel N, Kaur N, Doetsch P, Shadel G, et al. Checkpoint kinase phosphorylation in response to endogenous oxidative DNA damage in repair-deficient stationary-phase Saccharomyces cerevisiae. Mech Ageing Dev. 2009;130:501-8 pubmed publisher
    ..Single-strand resection may be accelerated by unrepaired oxidative base damage in the vicinity of a double-strand break. ..
  27. Branzei D, Seki M, Onoda F, Enomoto T. The product of Saccharomyces cerevisiae WHIP/MGS1, a gene related to replication factor C genes, interacts functionally with DNA polymerase delta. Mol Genet Genomics. 2002;268:371-86 pubmed
    ..Possible roles of Mgs1, DNA polymerase delta, Rad18 and Mms2 in replication and replication fork restart are discussed. ..
  28. Scheller J, Schürer A, Rudolph C, Hettwer S, Kramer W. MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of the genome from spontaneous and chemically induced damage. Genetics. 2000;155:1069-81 pubmed
    ..Epistasis analyses were carried out with representative mutants from various repair pathways (msh6, mag1, apn1, rad14, rad52, rad6, mms2, and rev3)...
  29. Morey N, Doetsch P, Jinks Robertson S. Delineating the requirements for spontaneous DNA damage resistance pathways in genome maintenance and viability in Saccharomyces cerevisiae. Genetics. 2003;164:443-55 pubmed
    ..In diploids, the presence of PRR alone may confer a lethal mutation load or, alternatively, PRR alone may be insufficient to deal with potentially lethal, replication-blocking lesions. ..
  30. Ramotar D, Kim C, Lillis R, Demple B. Intracellular localization of the Apn1 DNA repair enzyme of Saccharomyces cerevisiae. Nuclear transport signals and biological role. J Biol Chem. 1993;268:20533-9 pubmed
    The Apn1 DNA repair enzyme of Saccharomyces cerevisiae acts on abasic sites and oxygen radical damages...
  31. Steininger S, Ahne F, Winkler K, Kleinschmidt A, Eckardt Schupp F, Moertl S. A novel function for the Mre11-Rad50-Xrs2 complex in base excision repair. Nucleic Acids Res. 2010;38:1853-65 pubmed publisher
    ..Reduced gap-filling activity and the missing effect of aphidicoline treatment, an inhibitor for polymerases, on the BER efficiency indicate an involvement of the MRX complex in providing efficient polymerase activity. ..
  32. Ishchenko A, Ide H, Ramotar D, Nevinsky G, Saparbaev M. Alpha-anomeric deoxynucleotides, anoxic products of ionizing radiation, are substrates for the endonuclease IV-type AP endonucleases. Biochemistry. 2004;43:15210-6 pubmed
    ..Here we report that alphadA when present in DNA is recognized by the Saccharomyces cerevisiae Apn1 protein, a homologue of Nfo. Furthermore, alphaT is a substrate for Nfo and Apn1...
  33. Sarangi P, Altmannova V, Holland C, Bartosova Z, Hao F, Anrather D, et al. A versatile scaffold contributes to damage survival via sumoylation and nuclease interactions. Cell Rep. 2014;9:143-52 pubmed publisher
    ..These effects of Saw1 and its sumoylation suggest that Saw1 is a multifunctional scaffold that can facilitate diverse types of DNA repair through its modification and nuclease interactions. ..
  34. Yu S, Lee S, Johnson R, Prakash L, Prakash S. The stalling of transcription at abasic sites is highly mutagenic. Mol Cell Biol. 2003;23:382-8 pubmed
    ..From the various observations presented here, we infer that the stalling of transcription at AP sites is highly mutagenic. ..
  35. Lefevre S, Brossas C, Auchère F, Boggetto N, Camadro J, Santos R. Apn1 AP-endonuclease is essential for the repair of oxidatively damaged DNA bases in yeast frataxin-deficient cells. Hum Mol Genet. 2012;21:4060-72 pubmed publisher
    ..stress in frataxin-deficient yeast cells (?yfh1 mutant) is damage to nuclear DNA and that repair requires the Apn1 AP-endonuclease of the base excision repair pathway...
  36. Schürer K, Rudolph C, Ulrich H, Kramer W. Yeast MPH1 gene functions in an error-free DNA damage bypass pathway that requires genes from Homologous recombination, but not from postreplicative repair. Genetics. 2004;166:1673-86 pubmed
    ..On the contrary, in an sgs1 background we found a pronounced hyperrecombination phenotype. Thus, we propose that MPH1 is involved in a branch of homologous recombination that is specifically dedicated to error-free bypass. ..
  37. Liu C, Pouliot J, Nash H. Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1. Proc Natl Acad Sci U S A. 2002;99:14970-5 pubmed
    ..Despite finding that the yeast Apn1 protein has a Tdp1-like biochemical activity, genetic inactivation of all known yeast apurinic endonucleases does ..
  38. Morris L, Degtyareva N, Sheppard C, Heyburn L, Ivanov A, Kow Y, et al. Saccharomyces cerevisiae Apn1 mutation affecting stable protein expression mimics catalytic activity impairment: implications for assessing DNA repair capacity in humans. DNA Repair (Amst). 2012;11:753-65 pubmed publisher
    ..in an unbiased forward genetic screen to identify amino acid substitutions in the major yeast AP endonuclease, Apn1, that impair cellular DNA repair capacity by conferring sensitivity to the DNA alkylating agent methyl ..
  39. Johnson A, Demple B. Yeast DNA diesterase for 3'-fragments of deoxyribose: purification and physical properties of a repair enzyme for oxidative DNA damage. J Biol Chem. 1988;263:18009-16 pubmed
    ..This is a novel enzyme, whose N-terminal amino acid sequence does not show any significant similarity to published sequences, and which is not the product of any gene in the RAD52 epistasis group. ..
  40. Daley J, Wilson T, Ramotar D. Genetic interactions between HNT3/Aprataxin and RAD27/FEN1 suggest parallel pathways for 5' end processing during base excision repair. DNA Repair (Amst). 2010;9:690-9 pubmed publisher
    ..Surprisingly, HNT3 deletion partially rescued H(2)O(2) sensitivity in recombination-deficient rad51Delta and rad52Delta cells, suggesting that Hnt3 promotes formation of a repair intermediate that is resolved by recombination. ..
  41. Jilani A, Vongsamphanh R, Leduc A, Gros L, Saparbaev M, Ramotar D. Characterization of two independent amino acid substitutions that disrupt the DNA repair functions of the yeast Apn1. Biochemistry. 2003;42:6436-45 pubmed
    The members of the Endo IV family of DNA repair enzymes, including Saccharomyces cerevisiae Apn1 and Escherichia coli endonuclease IV, possess the capacity to cleave abasic sites and to remove 3'-blocking groups at single-strand breaks ..
  42. Rusyn I, Fry R, Begley T, Klapacz J, Svensson J, Ambrose M, et al. Transcriptional networks in S. cerevisiae linked to an accumulation of base excision repair intermediates. PLoS ONE. 2007;2:e1252 pubmed
    ..number of abasic sites is significantly increased when the 3-methyladenine DNA glycosylase (Mag): AP endonuclease (Apn1) ratio is increased and that spontaneous frame shift mutation is considerably elevated when either Mag, or Mag plus ..
  43. Lazzaro F, Novarina D, Amara F, Watt D, Stone J, Costanzo V, et al. RNase H and postreplication repair protect cells from ribonucleotides incorporated in DNA. Mol Cell. 2012;45:99-110 pubmed publisher
  44. Pogorzala L, Mookerjee S, Sia E. Evidence that msh1p plays multiple roles in mitochondrial base excision repair. Genetics. 2009;182:699-709 pubmed publisher
    ..In addition to this separation of function, we also found that the role of Msh1p in BER is unlikely to be involved in the avoidance of large-scale deletions and rearrangements. ..
  45. Kaniak A, Dzierzbicki P, Rogowska A, Malc E, Fikus M, Ciesla Z. Msh1p counteracts oxidative lesion-induced instability of mtDNA and stimulates mitochondrial recombination in Saccharomyces cerevisiae. DNA Repair (Amst). 2009;8:318-29 pubmed publisher
    ..We also show that double mutants carrying the msh1-R813W allele, combined with deletion of either OGG1 or APN1, the latter resulting in deficiency of the Apn1 endonuclease, exhibit a synergistic effect on the frequency of ..
  46. Maclean M, Aamodt R, Harris N, Alseth I, Seeberg E, Bjørås M, et al. Base excision repair activities required for yeast to attain a full chronological life span. Aging Cell. 2003;2:93-104 pubmed
    ..They also reveal an appreciable overlap in the G0 maintenance functions of the different BER DNA glycosylases and AP endonucleases. ..
  47. Odagiri N, Seki M, Onoda F, Yoshimura A, Watanabe S, Enomoto T. Budding yeast mms4 is epistatic with rad52 and the function of Mms4 can be replaced by a bacterial Holliday junction resolvase. DNA Repair (Amst). 2003;2:347-58 pubmed
  48. Flott S, Alabert C, Toh G, Toth R, Sugawara N, Campbell D, et al. Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand annealing mode of DNA repair in budding yeast. Mol Cell Biol. 2007;27:6433-45 pubmed
    ..These results indicate that Slx4 has multiple functions in responding to DNA damage and that a subset of these are regulated by Mec1/Tel1-dependent phosphorylation. ..
  49. Boiteux S, Guillet M. Use of yeast for detection of endogenous abasic lesions, their source, and their repair. Methods Enzymol. 2006;408:79-91 pubmed
    ..Data shows that the simultaneous inactivation of two AP endonucleases (Apn1 and Apn2) and of the nuclease Rad1-Rad10 causes cell death in Saccharomyces cerevisiae...