Disabling the Fanconi Anemia Pathway in Stem Cells Leads to Radioresistance and Genomic Instability.

ABSTRACT: Fanconi anemia is an inherited genome instability syndrome characterized by interstrand cross-link hypersensitivity, congenital defects, bone marrow failure, and cancer predisposition. Although DNA repair mediated by Fanconi anemia genes has been extensively studied, how inactivation of these genes leads to specific cellular phenotypic consequences associated with Fanconi anemia is not well understood. Here we report that Fanconi anemia stem cells in the C. elegans germline and in murine embryos display marked nonhomologous end joining (NHEJ)-dependent radiation resistance, leading to survival of progeny cells carrying genetic lesions. In contrast, DNA cross-linking does not induce generational genomic instability in Fanconi anemia stem cells, as widely accepted, but rather drives N

SUBMITTER: Deng X 

PROVIDER: S-EPMC8445591 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature