Isoforms of Base Excision Repair Enzymes Produced by Alternative Splicing

Transcripts of many enzymes involved in base excision repair (BER) undergo extensive alternative splicing, but functions of the corresponding alternative splice variants remain largely unexplored. In this review, we cover the studies describing the common alternatively spliced isoforms and disease-associated variants of DNA glycosylases, AP-endonuclease 1, and DNA polymerase beta. We also discuss the roles of alternative splicing in the regulation of their expression, catalytic activities, and intracellular transport.

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Effect of DNA Glycosylases OGG1 and Neil1 on Oxidized G-Rich Motif in the KRAS Promoter

International Journal of Molecular Sciences ◽

10.3390/ijms22031137 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1137

Author(s):

Annalisa Ferino ◽

Luigi E. Xodo

Keyword(s):

Oxidative Stress ◽

Base Excision Repair ◽

Excision Repair ◽

Start Site ◽

Dna Glycosylases ◽

Repair Pathway ◽

Transcription Start ◽

G Quadruplex ◽

Base Excision ◽

Regulatory Functions

The promoter of the Kirsten ras (KRAS) proto-oncogene contains, upstream of the transcription start site, a quadruplex-forming motif called 32R with regulatory functions. As guanine under oxidative stress can be oxidized to 8-oxoguanine (8OG), we investigated the capacity of glycosylases 8-oxoguanine glycosylase (OGG1) and endonuclease VIII-like 1 (Neil1) to excise 8OG from 32R, either in duplex or G-quadruplex (G4) conformation. We found that OGG1 efficiently excised 8OG from oxidized 32R in duplex but not in G4 conformation. By contrast, glycosylase Neil1 showed more activity on the G4 than the duplex conformation. We also found that the excising activity of Neil1 on folded 32R depended on G4 topology. Our data suggest that Neil1, besides being involved in base excision repair pathway (BER), could play a role on KRAS transcription.

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Oxidative base damage to DNA: specificity of base excision repair enzymes

Mutation Research/Reviews in Mutation Research ◽

10.1016/s1383-5742(00)00022-3 ◽

2000 ◽

Vol 462 (2-3) ◽

pp. 121-128 ◽

Cited By ~ 75

Author(s):

Jean Cadet ◽

Anne-Gaëlle Bourdat ◽

Cédric D'Ham ◽

Victor Duarte ◽

Didier Gasparutto ◽

...

Keyword(s):

Base Excision Repair ◽

Excision Repair ◽

Base Damage ◽

Repair Enzymes ◽

Base Excision ◽

Dna Specificity ◽

Oxidative Base Damage

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Processing of the abasic sites clustered with the benzo[a]pyrene adducts by the base excision repair enzymes

DNA Repair ◽

10.1016/j.dnarep.2016.12.007 ◽

2017 ◽

Vol 50 ◽

pp. 43-53 ◽

Cited By ~ 2

Author(s):

Lidia V. Starostenko ◽

Nadejda I. Rechkunova ◽

Natalia A. Lebedeva ◽

Alexander A. Lomzov ◽

Vladimir V. Koval ◽

...

Keyword(s):

Base Excision Repair ◽

Excision Repair ◽

Abasic Sites ◽

Repair Enzymes ◽

Base Excision

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Formation of cytosine glycol and 5,6-dihydroxycytosine in deoxyribonucleic acid on treatment with osmium tetroxide

Biochemical Journal ◽

10.1042/bj2350531 ◽

1986 ◽

Vol 235 (2) ◽

pp. 531-536 ◽

Cited By ~ 76

Author(s):

M Dizdaroglu ◽

E Holwitt ◽

M P Hagan ◽

W F Blakely

Keyword(s):

Dna Repair ◽

Formic Acid ◽

Excision Repair ◽

Dna Lesions ◽

Gas Chromatography Mass Spectrometry ◽

Dna Glycosylases ◽

Thymine Glycol ◽

Repair Enzymes ◽

Base Excision

OsO4 selectively forms thymine glycol lesions in DNA. In the past, OsO4-treated DNA has been used as a substrate in studies of DNA repair utilizing base-excision repair enzymes such as DNA glycosylases. There is, however, no information available on the chemical identity of other OsO4-induced base lesions in DNA. A complete knowledge of such DNA lesions may be of importance for repair studies. Using a methodology developed recently for characterization of oxidative base damage in DNA, we provide evidence for the formation of cytosine glycol and 5,6-dihydroxycytosine moieties, in addition to thymine glycol, in DNA on treatment with OsO4. For this purpose, samples of OsO4-treated DNA were hydrolysed with formic acid, then trimethylsilylated and analysed by capillary gas chromatography-mass spectrometry. In addition to thymine glycol, 5-hydroxyuracil (isobarbituric acid), 5-hydroxycytosine and 5,6-dihydroxyuracil (isodialuric acid or dialuric acid) were identified in OsO4-treated DNA. It is suggested that 5-hydroxyuracil was formed by formic acid-induced deamination and dehydration of cytosine glycol, which was the actual oxidation product of the cytosine moiety in DNA. 5-Hydroxycytosine obviously resulted from dehydration of cytosine glycol, and 5,6-dihydroxyuracil from deamination of 5,6-dihydroxycytosine. This scheme was supported by the presence of 5-hydroxyuracil, uracil glycol and 5,6-dihydroxyuracil in OsO4-treated cytosine. Treatment of OsO4-treated cytosine with formic acid caused the complete conversion of uracil glycol into 5-hydroxyuracil. The implications of these findings relative to studies of DNA repair are discussed.

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