Single-nucleotide polymorphism of the DNA cytosine deaminase APOBEC3H haplotype I leads to enzyme destabilization and correlates with lung cancer.

ABSTRACT: A number of APOBEC family DNA cytosine deaminases can induce mutations in tumor cells. APOBEC3H haplotype I is one of the deaminases that has been proposed to cause mutations in lung cancer. Here, we confirmed that APOBEC3H haplotype I can cause uracil-induced DNA damage in lung cancer cells that results in γH2AX foci. Interestingly, the database of cancer biomarkers in DNA repair genes (DNArCdb) identified a single-nucleotide polymorphism (rs139298) of APOBEC3H haplotype I that is involved in lung cancer. While we thought this may increase the activity of APOBEC3H haplotype I, instead we found through computational modeling and cell-based experiments that this single-nucleotide polymorphism causes the destabilization of APOBEC3H Haplotype I. Computational analysis suggests that the result

SUBMITTER: Hix MA 

PROVIDER: S-EPMC7503452 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature