Structural and functional impact of the POLD1 Ser605del variant in MDPL syndrome: insights from protein-protein interactions.

ABSTRACT:

Background

Mandibular hypoplasia, Deafness, Progeroid features, and Lipodystrophy (MDPL) syndrome is a very rare genetic disorder linked to variants in the POLD1 gene, which encodes the catalytic subunit of DNA polymerase delta, a key enzyme involved in DNA replication and repair. Most patients carry a recurrent in frame deletion (p.Ser605del) within the active site of the p125 subunit. Despite its rarity, understanding the functional consequences of the Ser605del variant has broad implications for aging-related diseases and genome stability.

Methods

We combined structural modelling, molecular dynamics simulations, and protein-protein interaction (PPIs) analyses to evaluate the impact of Ser605del in the catalytic activity of DNA polymerase delta. Bioinformatic tools were ap

SUBMITTER: Murdocca M 

PROVIDER: S-EPMC12606881 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature