DNA polymerase ι compensates for Fanconi anemia pathway deficiency by countering DNA replication stress.

ABSTRACT: Fanconi anemia (FA) is caused by defects in cellular responses to DNA crosslinking damage and replication stress. Given the constant occurrence of endogenous DNA damage and replication fork stress, it is unclear why complete deletion of FA genes does not have a major impact on cell proliferation and germ-line FA patients are able to progress through development well into their adulthood. To identify potential cellular mechanisms that compensate for the FA deficiency, we performed dropout screens in FA mutant cells with a whole genome guide RNA library. This uncovered a comprehensive genome-wide profile of FA pathway synthetic lethality, including POLI and CDK4 As little is known of the cellular function of DNA polymerase iota (Pol ι), we focused on its role in the loss-of-fun

SUBMITTER: Wang R 

PROVIDER: S-EPMC7777187 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature