The molecular origin of the MMR-dependent apoptosis pathway from dynamics analysis of MutSα-DNA complexes.

ABSTRACT: The cellular response to DNA damage signaling by mismatch-repair (MMR) proteins is incompletely understood. It is generally accepted that MMR-dependent apoptosis pathway in response to DNA damage detection is independent of MMR's DNA repair function. In this study, we investigate correlated motions in response to the binding of mismatched and platinum cross-linked DNA fragments by MutSα, as derived from 50 ns molecular dynamics simulations. The protein dynamics in response to the mismatched and damaged DNA recognition suggests that MutSα signals their recognition through independent pathways providing evidence for the molecular origin of the MMR-dependent apoptosis. MSH2 subunit is indicated to play a key role in signaling both mismatched and damaged DNA recognition; localized and collecti

SUBMITTER: Negureanu L 

PROVIDER: S-EPMC3389999 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature