The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom's syndrome helicase for efficient disruption of D-loops.

ABSTRACT: Homologous recombination (HR) is a ubiquitous and efficient process that serves the repair of severe forms of DNA damage and the generation of genetic diversity during meiosis. HR can proceed via multiple pathways with different outcomes that may aid or impair genome stability and faithful inheritance, underscoring the importance of HR quality control. Human Bloom's syndrome (BLM, RecQ family) helicase plays central roles in HR pathway selection and quality control via unexplored molecular mechanisms. Here we show that BLM's multi-domain structural architecture supports a balance between stabilization and disruption of displacement loops (D-loops), early HR intermediates that are key targets for HR regulation. We find that this balance is markedly shifted toward efficient D-loop disruption

SUBMITTER: Harami GM 

PROVIDER: S-EPMC8813930 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature