RAD50 missense variants differentially affect the DNA damage response and mitotic progression.

ABSTRACT: RAD50 is the central protein of the MRN complex and crucial in DNA double-strand break repair. RAD50 deficiency causes a genomic instability disorder characterized by microcephaly and stunted growth. Using lentiviral constructs, we investigated whether cancer-related RAD50 missense variants can complement the delayed damage response after exposure to the chemotherapeutic agent epirubicin and/or mitotic progression in RAD50-deficient fibroblasts. Eight missense variants, all capable of forming an MRN complex, supported the DNA damage response and mitotic features to different extents, indicating these functions are separable. Three variants showed both an impaired epirubicin response and slowed cell division in the likely pathogenic range. Assessing RAD50 missense variants with distinct fun

SUBMITTER: Redeker H 

PROVIDER: S-EPMC12720227 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature