Mechanism of CRL4Cdt2, a PCNA-dependent E3 ubiquitin ligase
- 1 August 2011
- journal article
- review article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 25 (15), 1568-1582
- https://doi.org/10.1101/gad.2068611
Abstract
Eukaryotic cell cycle transitions are driven by E3 ubiquitin ligases that catalyze the ubiquitylation and destruction of specific protein targets. For example, the anaphase-promoting complex/cyclosome (APC/C) promotes the exit from mitosis via destruction of securin and mitotic cyclins, whereas CRL1Skp2 allows entry into S phase by targeting the destruction of the cyclin-dependent kinase (CDK) inhibitor p27. Recently, an E3 ubiquitin ligase called CRL4Cdt2 has been characterized, which couples proteolysis to DNA synthesis via an unusual mechanism that involves display of substrate degrons on the DNA polymerase processivity factor PCNA. Through its destruction of Cdt1, p21, and Set8, CRL4Cdt2 has emerged as a master regulator that prevents rereplication in S phase. In addition, it also targets other factors such as E2F and DNA polymerase η. In this review, we discuss our current understanding of the molecular mechanism of substrate recognition by CRL4Cdt2 and how this E3 ligase helps to maintain genome integrity.Keywords
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