Alkylated DNA repair by a novel HhH-GPD family protein from Crenarchaea.

ABSTRACT: HhH-GPD (helix-hairpin-helix-glycine/proline/aspartate) family proteins are involved in DNA damage repair. Currently, mechanism of alkylated DNA repair in Crenarchaea has not been fully clarified. The hyperthermophilic model crenarchaeon Saccharolobus islandicus REY15A possesses a novel HhH-GPD family protein (Sis-HhH-GPD), where its Ser152 corresponds to a conserved catalytic Asp in other HhH-GPD homologs. Herein, we report that Sis-HhH-GPD is a novel bi-functional glycosylase, capable of removing both 1-methyladenine (1-meA) from DNA and alkylated bases from DNA created by methyl methanesulfonate (MMS). Mutational analyses show that E134 is essential for catalysis, whereas S152 is not essential. Sis-HhH-GPD might utilize aromatic rings of Y154 and W57 to stack against 1-meA base for flip

SUBMITTER: Zhang L 

PROVIDER: S-EPMC11754123 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature