FZR1
Description
The FZR1 (fizzy and cell division cycle 20 related 1) is a protein-coding gene located on chromosome 19.
Fizzy-related protein homolog, also known as hCDH1, is a protein that in humans is encoded by the FZR1 gene. FZR1 has been shown to interact with CDC27 and FBXO5.
FZR1 acts as a substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. It associates with the APC/C in late mitosis, replacing CDC20 and activating the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates, preventing the accumulation of positive regulators of the cell cycle. At the G1/S transition, FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, FZR1 is required for the G2 DNA damage checkpoint. Dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. FZR1 acts as an adapter for APC/C, targeting the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through regulation of RBBP8/CtIP protein turnover, FZR1 may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR).
FZR1 is also known as CDC20C, CDH1, DEE109, FZR, FZR2, HCDH, HCDH1.
