Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

ABSTRACT DNA damage is unavoidable, and organisms across the evolutionary spectrum possess DNA repair pathways that are critical for cell viability and genomic stability. To understand the role of base excision repair (BER) in protecting eukaryotic cells against alkylating agents, we generated Schizosaccharomyces pombe strains mutant for the mag1 3-methyladenine DNA glycosylase gene. We report that S. pombe mag1 mutants have only a slightly increased sensitivity to methylation damage, suggesting that Mag1-initiated BER plays a surprisingly minor role in alkylation resistance in this organism. We go on to show that other DNA repair pathways play a larger role than BER in alkylation resistance. Mutations in genes involved in nucleotide excision repair (rad13) and recombinational repair (rhp51) are much more alkylation sensitive thanmag1 mutants. In addition, S. pombe mutant for the flap endonuclease rad2 gene, whose precise function in DNA repair is unclear, were also more alkylation sensitive thanmag1 mutants. Further, mag1 andrad13 interact synergistically for alkylation resistance, and mag1 and rhp51 display a surprisingly complex genetic interaction. A model for the role of BER in the generation of alkylation-induced DNA strand breaks in S. pombe is discussed.

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The involvement of nucleotide excision repair proteins in the removal of oxidative DNA damage

Nucleic Acids Research ◽

10.1093/nar/gkaa777 ◽

2020 ◽

Vol 48 (20) ◽

pp. 11227-11243 ◽

Cited By ~ 1

Author(s):

Namrata Kumar ◽

Sripriya Raja ◽

Bennett Van Houten

Keyword(s):

Nucleotide Excision Repair ◽

Base Excision Repair ◽

Oxidative Dna Damage ◽

Excision Repair ◽

Base Damage ◽

The Past ◽

Nucleotide Excision ◽

Oxidative Processes ◽

Repair Pathways ◽

Base Excision

Abstract The six major mammalian DNA repair pathways were discovered as independent processes, each dedicated to remove specific types of lesions, but the past two decades have brought into focus the significant interplay between these pathways. In particular, several studies have demonstrated that certain proteins of the nucleotide excision repair (NER) and base excision repair (BER) pathways work in a cooperative manner in the removal of oxidative lesions. This review focuses on recent data showing how the NER proteins, XPA, XPC, XPG, CSA, CSB and UV-DDB, work to stimulate known glycosylases involved in the removal of certain forms of base damage resulting from oxidative processes, and also discusses how some oxidative lesions are probably directly repaired through NER. Finally, since many glycosylases are inhibited from working on damage in the context of chromatin, we detail how we believe UV-DDB may be the first responder in altering the structure of damage containing-nucleosomes, allowing access to BER enzymes.

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Role of Nucleotide Excision Repair or Base Excision Repair in Movement of Various n-Alkylated Bases, Investigated by the Comet Assay

Genes and Environment ◽

10.3123/jemsge.2013.012 ◽

2014 ◽

Vol 36 (1) ◽

pp. 10-16 ◽

Cited By ~ 2

Author(s):

Chihiro Odajima ◽

Takanori Nakamura ◽

Maki Nakamura ◽

Masanori Miura ◽

Kayoko Yamasaki ◽

...

Keyword(s):

Comet Assay ◽

Nucleotide Excision Repair ◽

Base Excision Repair ◽

Excision Repair ◽

Nucleotide Excision ◽

Base Excision

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Regulation of DNA repair in serum-stimulated xeroderma pigmentosum cells.

The Journal of Cell Biology ◽

10.1083/jcb.99.4.1275 ◽

1984 ◽

Vol 99 (4) ◽

pp. 1275-1281 ◽

Cited By ~ 6

Author(s):

P K Gupta ◽

M A Sirover

Keyword(s):

Dna Repair ◽

Dna Synthesis ◽

Nucleotide Excision Repair ◽

Base Excision Repair ◽

Xeroderma Pigmentosum ◽

Excision Repair ◽

Nucleotide Excision ◽

Normal Human ◽

Complementation Groups ◽

Base Excision

The regulation of DNA repair during serum stimulation of quiescent cells was examined in normal human cells, in fibroblasts from three xeroderma pigmentosum complementation groups (A, C, and D), in xeroderma pigmentosum variant cells, and in ataxia telangiectasia cells. The regulation of nucleotide excision repair was examined by exposing cells to ultraviolet irradiation at discrete intervals after cell stimulation. Similarly, base excision repair was quantitated after exposure to methylmethane sulfonate. WI-38 normal human diploid fibroblasts, xeroderma pigmentosum variant cells, as well as ataxia telangiectasia cells enhanced their capacity for both nucleotide excision repair and for base excision repair prior to their enhancement of DNA synthesis. Further, in each cell strain, the base excision repair enzyme uracil DNA glycosylase was increased prior to the induction of DNA polymerase using the identical cells to quantitate each activity. In contrast, each of the three xeroderma complementation groups that were examined failed to increase their capacity for nucleotide excision repair above basal levels at any interval examined. This result was observed using either unscheduled DNA synthesis in the presence of 10 mM hydroxyurea or using repair replication in the absence of hydroxyurea to quantitate DNA repair. However, each of the three complementation groups normally regulated the enhancement of base excision repair after methylmethane sulfonate exposure and each induced the uracil DNA glycosylase prior to DNA synthesis. These results suggest that there may be a relationship between the sensitivity of xeroderma pigmentosum cells from each complementation group to specific DNA damaging agents and their inability to regulate nucleotide excision repair during cell stimulation.

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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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Yeast RAD26, a Homolog of the Human CSB Gene, Functions Independently of Nucleotide Excision Repair and Base Excision Repair in Promoting Transcription through Damaged Bases

Molecular and Cellular Biology ◽

10.1128/mcb.22.12.4383-4389.2002 ◽

2002 ◽

Vol 22 (12) ◽

pp. 4383-4389 ◽

Cited By ~ 37

Author(s):

Sung-Keun Lee ◽

Sung-Lim Yu ◽

Louise Prakash ◽

Satya Prakash

Keyword(s):

Rna Polymerase Ii ◽

Nucleotide Excision Repair ◽

Base Excision Repair ◽

Excision Repair ◽

Dna Lesions ◽

Nucleotide Excision ◽

Severe Reduction ◽

Base Excision ◽

Group B

ABSTRACT RAD26 in the yeast Saccharomyces cerevisiae is the counterpart of the human Cockayne syndrome group B (CSB) gene. Both RAD26 and CSB act in the preferential repair of UV lesions on the transcribed strand, and in this process, they function together with the components of nucleotide excision repair (NER). Here, we examine the role of RAD26 in the repair of DNA lesions induced upon treatment with the alkylating agent methyl methanesulfonate (MMS). MMS-induced DNA lesions include base damages such as 3-methyl adenine and 7-methyl guanine, and these lesions are removed in yeast by the alternate competing pathways of base excision repair (BER), which is initiated by the action of MAG1-encoded N-methyl purine DNA glycosylase, and NER. Interestingly, a synergistic increase in MMS sensitivity was observed in the rad26Δ strain upon inactivation of NER or BER, indicating that RAD26 promotes the survival of MMS-treated cells by a mechanism that acts independently of either of these repair pathways. The galactose-inducible transcription of the GAL2, GAL7, and GAL10 genes is reduced in MMS-treated rad26Δ cells and also in mag1Δ rad14Δ cells, whereas a very severe reduction in transcription occurs in MMS-treated mag1Δ rad14Δ rad26Δ cells. From these observations, we infer that RAD26 plays a role in promoting transcription by RNA polymerase II through damaged bases. The implications of these observations are discussed in this paper.

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