Deep structure-function analysis of the endonuclease Mus81 with dominant mutational scanning.

ABSTRACT: Protein structure-function relationships are critical for understanding molecular mechanisms and the impacts of genetic variation. Mutational scanning approaches can deliver scalable analysis, usually through the study of loss-of-function variants. Rarer dominant negative and gain-of-function variants can be more information rich, as they retain a stable proteoform and can be used to dissect molecular function while retaining biological context. Dominant variant proteoforms can still engage substrates and interact with binding partners. Here, we probe the structure-function relationships of the Mus81 endonuclease by ectopic expression of deep mutational scanning libraries to find amino acid variants that confer dominant sensitivity to genotoxic stress and dominant synthetic lethality. Scre

SUBMITTER: Oppedisano A 

PROVIDER: S-EPMC12207449 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature