Cyclin-dependent Kinase 1 (CDK1)-dependent Inhibition of the E3 Ubiquitin Ligase, CRL4CDT2, Ensures Robust Transition from S Phase to Mitosis.

Replication-coupled destruction of a cohort of cell cycle proteins ensures efficient and precise genome duplication. Three proteins destroyed during replication via the CRL4(CDT2) ubiquitin E3 ligase, CDT1, p21, and SET8 (PR-SET7), are also essential or important during mitosis making their re-accumulation after S phase a critical cell cycle event. During ...
early and mid-S phase and during DNA repair, PCNA loading onto DNA (PCNA(DNA)) triggers the interaction between CRL4(CDT2) and its substrates resulting in their degradation. We have discovered that beginning in late S phase, PCNA(DNA) is no longer sufficient to trigger CRL4(CDT2)-mediated degradation. A CDK1-dependent mechanism that blocks CRL4(CDT2) recruitment to chromatin actively protects CRL4(CDT2) substrates. We postulate that deliberate override of replication-coupled destruction allows anticipatory accumulation in late S phase. We further show that (as for CDT1) de novo SET8 re-accumulation is important for normal mitotic progression. In this manner, CDK1-dependent CRL4(CDT2) inactivation contributes to efficient transition from S phase to mitosis.
J. Biol. Chem.
Date: Nov. 19, 2014
Download Curated Data For This Publication
169896
Switch View:
  • Interactions 1