Overlapping Specificities of Base Excision Repair, Nucleotide Excision Repair, Recombination, and Translesion Synthesis Pathways for DNA Base Damage in Saccharomyces cerevisiae

ABSTRACT The removal of oxidative damage from Saccharomyces cerevisiae DNA is thought to be conducted primarily through the base excision repair pathway. The Escherichia coliendonuclease III homologs Ntg1p and Ntg2p are S. cerevisiae N-glycosylase-associated apurinic/apyrimidinic (AP) lyases that recognize a wide variety of damaged pyrimidines (H. J. You, R. L. Swanson, and P. W. Doetsch, Biochemistry 37:6033–6040, 1998). The biological relevance of theN-glycosylase-associated AP lyase activity in the repair of abasic sites is not well understood, and the majority of AP sites in vivo are thought to be processed by Apn1p, the major AP endonuclease in yeast. We have found that yeast cells simultaneously lacking Ntg1p, Ntg2p, and Apn1p are hyperrecombinogenic (hyper-rec) and exhibit a mutator phenotype but are not sensitive to the oxidizing agents H2O2 and menadione. The additional disruption of the RAD52 gene in the ntg1 ntg2 apn1 triple mutant confers a high degree of sensitivity to these agents. The hyper-rec and mutator phenotypes of the ntg1 ntg2 apn1 triple mutant are further enhanced by the elimination of the nucleotide excision repair pathway. In addition, removal of either the lesion bypass (Rev3p-dependent) or recombination (Rad52p-dependent) pathway specifically enhances the hyper-rec or mutator phenotype, respectively. These data suggest that multiple pathways with overlapping specificities are involved in the removal of, or tolerance to, spontaneous DNA damage in S. cerevisiae. In addition, the fact that these responses to induced and spontaneous damage depend upon the simultaneous loss of Ntg1p, Ntg2p, and Apn1p suggests a physiological role for the AP lyase activity of Ntg1p and Ntg2p in vivo.

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Involvement of two endonuclease III homologs in the base excision repair pathway for the processing of DNA alkylation damage in Saccharomyces cerevisiae

DNA Repair ◽

10.1016/j.dnarep.2003.09.005 ◽

2004 ◽

Vol 3 (1) ◽

pp. 51-59 ◽

Cited By ~ 30

Author(s):

Michelle Hanna ◽

Barbara L Chow ◽

Natalie J Morey ◽

Sue Jinks-Robertson ◽

Paul W Doetsch ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Base Excision Repair ◽

Excision Repair ◽

Dna Alkylation ◽

Repair Pathway ◽

Base Excision Repair Pathway ◽

Alkylation Damage ◽

Endonuclease Iii ◽

Base Excision

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Synergism between base excision repair, mediated by the DNA glycosylases Ntg1 and Ntg2, and nucleotide excision repair in the removal of oxidatively damaged DNA bases in Saccharomyces cerevisiae

Molecular Genetics and Genomics ◽

10.1007/s004380100507 ◽

2001 ◽

Vol 265 (6) ◽

pp. 1087-1096 ◽

Cited By ~ 41

Author(s):

L. Gellon ◽

R. Barbey ◽

P. Auffret van der Kemp ◽

D. Thomas ◽

S. Boiteux

Keyword(s):

Saccharomyces Cerevisiae ◽

Nucleotide Excision Repair ◽

Base Excision Repair ◽

Excision Repair ◽

Dna Bases ◽

Dna Glycosylases ◽

Nucleotide Excision ◽

Base Excision ◽

Damaged Dna

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Defects in base excision repair and homologous recombination, but not nucleotide excision repair, lead to altered cell cycle phase distributions in Saccharomyces cerevisiae

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.786.12 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Alejandro Oviedo ◽

Sarah Valencia ◽

Taylor R. DeForge ◽

O'taveon R. Fitzgerald ◽

L. Kevin Lewis

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Homologous Recombination ◽

Base Excision Repair ◽

Excision Repair ◽

Cell Cycle Phase ◽

Cycle Phase ◽

Nucleotide Excision ◽

Base Excision ◽

Altered Cell

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Early Steps in the DNA Base Excision Repair Pathway of a Fission YeastSchizosaccharomyces pombe

Journal of Nucleic Acids ◽

10.4061/2010/450926 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Kyoichiro Kanamitsu ◽

Shogo Ikeda

Keyword(s):

Base Excision Repair ◽

Excision Repair ◽

Alternative Pathway ◽

Strand Break ◽

Repair Pathway ◽

Single Strand Break ◽

Dna Base Excision Repair ◽

Dna Base ◽

Lyase Activity ◽

Base Excision

DNA base excision repair (BER) accounts for maintaining genomic integrity by removing damaged bases that are generated endogenously or induced by genotoxic agents. In this paper, we describe the roles of enzymes functioning in the early steps of BER in fission yeast. Although BER is an evolutionarily conserved process, some unique features of the yeast repair pathway were revealed by genetic and biochemical approaches. AP sites generated by monofunctional DNA glycosylases are incised mainly by AP lyase activity of Nth1p, a sole bifunctional glycosylase in yeast, to leave a blocked3′end. The major AP endonuclease Apn2p functions predominantly in removing the3′block. Finally, a DNA polymerase fills the gap, and a DNA ligase seals the nick (Nth1p-dependent or short patch BER). Apn1p backs up Apn2p. In long patch BER, Rad2p endonuclease removes flap DNA containing a lesion after DNA synthesis. A UV-specific endonuclease Uve1p engages in an alternative pathway by nicking DNA on the5′side of oxidative damage. Nucleotide excision repair and homologous recombination are involved in repair of BER intermediates including the AP site and single-strand break with the3′block. Other enzymes working in3′end processing are also discussed.

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DNA Polymerase X of African Swine Fever Virus: Insertion Fidelity on Gapped DNA substrates and AP lyase Activity Support a Role in Base Excision Repair of Viral DNA

Journal of Molecular Biology ◽

10.1016/s0022-2836(03)00019-6 ◽

2003 ◽

Vol 326 (5) ◽

pp. 1403-1412 ◽

Cited By ~ 28

Author(s):

Ramón Garcı́a-Escudero ◽

Miguel Garcı́a-Dı́az ◽

Marı́a L Salas ◽

Luis Blanco ◽

José Salas

Keyword(s):

Dna Polymerase ◽

Base Excision Repair ◽

Excision Repair ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Viral Dna ◽

Lyase Activity ◽

Base Excision ◽

Ap Lyase ◽

Gapped Dna

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DNA repair in higher plants; photoreactivation is the major DNA repair pathway in non-proliferating cells while excision repair (nucleotide excision repair and base excision repair) is active in proliferating cells

Nucleic Acids Research ◽

10.1093/nar/gkh591 ◽

2004 ◽

Vol 32 (9) ◽

pp. 2760-2767 ◽

Cited By ~ 67

Author(s):

S. Kimura

Keyword(s):

Dna Repair ◽

Nucleotide Excision Repair ◽

Base Excision Repair ◽

Higher Plants ◽

Excision Repair ◽

Repair Pathway ◽

Proliferating Cells ◽

Nucleotide Excision ◽

Base Excision

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Histones participate in base excision repair of 8-oxodGuo by transiently cross-linking with active repair intermediates in nucleosome core particles

Nucleic Acids Research ◽

10.1093/nar/gkaa1153 ◽

2020 ◽

Author(s):

Mengtian Ren ◽

Mengdi Shang ◽

Huawei Wang ◽

Zhen Xi ◽

Chuanzheng Zhou

Keyword(s):

Base Excision Repair ◽

Oxidative Dna Damage ◽

Excision Repair ◽

Cross Linking ◽

Nucleosome Core ◽

Nucleosome Core Particles ◽

Lyase Activity ◽

Base Excision ◽

Ap Lyase ◽

Core Particles

Abstract 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) is a biomarker of oxidative DNA damage and can be repaired by hOGG1 and APE1 via the base excision repair (BER) pathway. In this work, we studied coordinated BER of 8-oxodGuo by hOGG1 and APE1 in nucleosome core particles and found that histones transiently formed DNA-protein cross-links (DPCs) with active repair intermediates such as 3′-phospho-α,β-unsaturated aldehyde (PUA) and 5′-deoxyribosephosphate (dRP). The effects of histone participation could be beneficial or deleterious to the BER process, depending on the circumstances. In the absence of APE1, histones enhanced the AP lyase activity of hOGG1 by cross-linking with 3′-PUA. However, the formed histone-PUA DPCs hampered the subsequent repair process. In the presence of APE1, both the AP lyase activity of hOGG1 and the formation of histone-PUA DPCs were suppressed. In this case, histones could catalyse removal of the 5′-dRP by transiently cross-linking with the active intermediate. That is, histones promoted the repair by acting as 5′-dRP lyases. Our findings demonstrate that histones participate in multiple steps of 8-oxodGuo repair in nucleosome core particles, highlighting the diverse roles that histones may play during DNA repair in eukaryotic cells.

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