論文 - 詳細
| RRC ID | 35260 |
|---|---|
| 著者 | Bharti SK, Varshney U. |
| タイトル | Analysis of the impact of a uracil DNA glycosylase attenuated in AP-DNA binding in maintenance of the genomic integrity in Escherichia coli. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
Uracil DNA glycosylase (Ung) initiates the uracil excision repair pathway. We have earlier characterized the Y66W and Y66H mutants of Ung and shown that they are compromised by approximately 7- and approximately 170-fold, respectively in their uracil excision activities. In this study, fluorescence anisotropy measurements show that compared with the wild-type, the Y66W protein is moderately compromised and attenuated in binding to AP-DNA. Allelic exchange of ung in Escherichia coli with ung::kan, ungY66H:amp or ungY66W:amp alleles showed approximately 5-, approximately 3.0- and approximately 2.0-fold, respectively increase in mutation frequencies. Analysis of mutations in the rifampicin resistance determining region of rpoB revealed that the Y66W allele resulted in an increase in A to G (or T to C) mutations. However, the increase in A to G mutations was mitigated upon expression of wild-type Ung from a plasmid borne gene. Biochemical and computational analyses showed that the Y66W mutant maintains strict specificity for uracil excision from DNA. Interestingly, a strain deficient in AP-endonucleases also showed an increase in A to G mutations. We discuss these findings in the context of a proposal that the residency of DNA glycosylase(s) onto the AP-sites they generate shields them until recruitment of AP-endonucleases for further repair. |
| 巻・号 | 38(7) |
| ページ | 2291-301 |
| 公開日 | 2010-4-1 |
| DOI | 10.1093/nar/gkp1210 |
| PII | gkp1210 |
| PMID | 20056657 |
| PMC | PMC2853124 |
| MeSH | Alleles Amino Acid Substitution DNA / metabolism* DNA Damage DNA Repair DNA-Directed RNA Polymerases Escherichia coli / enzymology Escherichia coli / genetics* Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism* Genome, Bacterial Mutation Uracil-DNA Glycosidase / genetics Uracil-DNA Glycosidase / metabolism* |
| IF | 11.502 |
| 引用数 | 8 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 原核生物(大腸菌) | |