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The role of cysteines in the structure and function of OGG1
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- 8-Oxoguanine glycosylase (OGG1) is a base excision repair enzyme responsible for the recognition and removal of 8-oxoguanine, a commonly occurring oxidized DNA modification. OGG1 prevents the accumulation of mutations and regulates the transcription of various oxidative stress-response genes. In addition to targeting DNA, oxidative stress can affect proteins like OGG1 itself, specifically at cysteine residues. Previous work has shown that the function of OGG1 is sensitive to oxidants, with the cysteine residues of OGG1 being the most likely site of oxidation. Due to the integral role of OGG1 in maintaining cellular homeostasis under oxidative stress, it is important to understand the effect of oxidants on OGG1 and the role of cysteines in its structure and function. In this study, we investigate the role of the cysteine residues in the function of OGG1 by mutating and characterizing each cysteine residue. Our results indicate that the cysteines in OGG1 fall into four functional categories: those that are necessary for (1) glycosylase activity (C146 and C255), (2) lyase activity (C140S, C163, C241, and C253), and (3) structural stability (C253) and (4) those with no known function (C28 and C75). These results suggest that under conditions of oxidative stress, cysteine can be targeted for modifications, thus altering the response of OGG1 and affecting its downstream cellular functions.
- Subjects :
- 0301 basic medicine
DNA Repair
DNA repair
Cellular homeostasis
Electrophoretic Mobility Shift Assay
IAEDANS, 5-({2-[(iodoacetyl)amino]ethyl}amino)naphthalene-1-sulfonic acid
base excision repair
Biochemistry
DNA Glycosylases
03 medical and health sciences
chemistry.chemical_compound
8-oxoguanine glycosylase
Cysteine
Lyase activity
BER, base excision repair
Molecular Biology
030102 biochemistry & molecular biology
8-oxoG, 8-oxoguanine
N-Ethylmaleimide
OGGI, 8-Oxoguanine glycosylase
Cell Biology
Base excision repair
8-Oxoguanine
Cell biology
Oxidative Stress
030104 developmental biology
chemistry
DNA glycosylase
NEM, N-ethylmaleimide
cysteine oxidation
PUA, α, β-polyunsaturated aldehyde
Oxidation-Reduction
THF, tetrahydrofuran
Research Article
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 296
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....a94ff0bbab5aae53d7cdbac8ed482214