PP2A licenses the FANCD2/FANCI complex for chromosome loading.

The Fanconi anemia (FA) pathway removes interstrand crosslinks (ICLs) between the Watson-Crick strands of the DNA double helix in humans. Central to the pathway is the FANCD2/FANCI complex, which must be loaded onto chromosomes. Here, we report the identification of a PP2A phosphatase complex, which specifically dephosphorylates an inhibitory cluster in FANCD2, thereby licensing its loading in response to DNA damage.

Biological and Pathological Implications of an Alternative ATP-Powered Proteasomal Assembly With Cdc48 and the 20S Peptidase.

The ATP-powered protein degradation machinery plays essential roles in maintaining protein homeostasis in all organisms. Robust proteolytic activities are typically sequestered within protein complexes to avoid the fatal removal of essential proteins. Because the openings of proteolytic chambers are narrow, substrate proteins must undergo unfolding.