Functional Evaluation of Nine Missense-Type Variants of the Human DNA Glycosylase Enzyme MUTYH in the Japanese Population
| Autor: | Haruhiko Sugimura, Hong Tao, Hidetaka Yamada, Kazuya Shinmura, Hisami Kato, Masanori Goto, Satoki Nakamura |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genotype Mutation Missense Biology medicine.disease_cause Cell Line DNA Glycosylases 03 medical and health sciences 0302 clinical medicine Germline mutation Asian People Japan MUTYH Genetics medicine Humans Missense mutation Allele Gene Alleles Genetic Association Studies Germ-Line Mutation Genetics (clinical) Mutation MUTYH-Associated Polyposis Enzyme Activation 030104 developmental biology Amino Acid Substitution DNA glycosylase 030220 oncology & carcinogenesis |
| Zdroj: | Human Mutation. 37:350-353 |
| ISSN: | 1059-7794 |
| DOI: | 10.1002/humu.22949 |
| Popis: | Biallelic germline mutations of MUTYH, the gene encoding DNA glycosylase, cause MUTYH-associated polyposis (MAP), characterized by multiple colorectal adenomas and carcinoma(s). However, a considerable number of MUTYH variants are still functionally uncharacterized. Herein, we report the results of functional evaluation of nine missense-type MUTYH variant proteins in the Japanese population. The DNA glycosylase activity and ability to suppress mutations caused by 8-hydroxyguanine, an oxidized form of guanine, were examined for the nine variants of type 2 MUTYH, a nuclear form of the enzyme, by DNA cleavage activity assay and supF forward mutation assay, respectively. Both activities were severely defective in the p.N210S MUTYH type 2 variant corresponding to p.N238S in the reference MUTYH form and partially defective in p.R219G variant corresponding to p.R247G, but nearly fully retained in seven other variants examined. Our results suggest that p.N238S and p.R247G are likely to be pathogenic alleles for MAP. |
| Databáze: | OpenAIRE |
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