Cullin 4A (CUL4A)

CUL4A is the ubiquitin ligase component of a multimeric complex involved in the degradation of DNA damage-response proteins. Human CUL4A and CUL4B are orthologs of nematode Cul4. The partial C-terminal amino acid sequences of CUL4A and CUL4B share 88% identity. Inactivation of CUL4 causes massive DNA rereplication, producing cells with up to 100C DNA content. The C. elegans ortholog of the replication-licensing factor Cdt1 is required for DNA replication. C. elegans CDT1 is present in G1-phase nuclei but disappears as cells enter S phase. In cells lacking CUL4, CDT1 levels failed to decrease during S phase and instead remained constant in the rereplicating cells. Removal of 1 genomic copy of CDT1 suppressed the CUL4 rereplication phenotype.