 CRL4A complexes regulate entry into the DNA synthesis phase, or S phase, of the mitotic cycle by regulating protein expression levels of the replication licensing factor protein Cdt1 and cyclin-dependent kinase inhibitor p21.In both cases, CRL4A utilizes Cdt2 as the DCAF to bind both substrates in a PCNA-dependent manner.During unperturbed cell cycle progression, ubiquitination and downregulation of these proteins by CRL4ACdt2 occurs at the onset of DNA replication.