FZR1A gene on chromosome 19p13.3 that encodes a key regulator of ligase activity of the anaphase-promoting complex/cyclosome (APC/C), conferring substrate specificity upon the complex. FZR1 associates with the APC/C in late mitosis (in place of CDC20) and activates the APC/C during anaphase and telophase. The APC/C degrades the substrate to ensure that cell cycle upregulators do not accumulate prematurely; at the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. FZR1 is highly expressed in the heart, liver, spleen, and in some cancer cell lines.
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