Human Polß Natural Polymorphic Variants G118V and R149I Affects Substate Binding and Catalysis.
Int J Mol Sci
; 24(6)2023 Mar 20.
Article
em En
| MEDLINE
| ID: mdl-36982964
DNA polymerase ß (Polß) expression is essential for the cell's response to DNA damage that occurs during natural cellular processes. Polß is considered the main reparative DNA polymerase, whose role is to fill the DNA gaps arising in the base excision repair pathway. Mutations in Polß can lead to cancer, neurodegenerative diseases, or premature aging. Many single-nucleotide polymorphisms have been identified in the POLB gene, but the consequences of these polymorphisms are not always clear. It is known that some polymorphic variants in the Polß sequence reduce the efficiency of DNA repair, thereby raising the frequency of mutations in the genome. In the current work, we studied two polymorphic variants (G118V and R149I separately) of human Polß that affect its DNA-binding region. It was found that each amino acid substitution alters Polß's affinity for gapped DNA. Each polymorphic variant also weakens its binding affinity for dATP. The G118V variant was found to greatly affect Polß's ability to fill gapped DNA and slowed the catalytic rate as compared to the wild-type enzyme. Thus, these polymorphic variants seem to decrease the ability of Polß to maintain base excision repair efficiency.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Reparo do DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article