May 28, 2020 · p21 Waf/CIP1 is a small unstructured protein that binds and inactivates cyclin-dependent kinases (CDKs). To this end, p21 levels increase following the activation of the p53 tumor suppressor. CDK inhibition by p21 triggers cell-cycle arrest in …

Apr 2, 2019 · Shape-based clustering revealed that the dynamics of the CDK inhibitor p21 diverges from the dynamics of its transcription factor p53 during S phase. Using mathematical modeling, we predict and experimentally validate that S phase-specific degradation of p21 by PCNA-CRL4 cdt2 is sufficient to explain these heterogeneous responses. This ...

PCNA seems to act as an important mediator of p21 function, which raises the mechanistic question of how p21 is able to regulate both the cell cycle and DNA replication. A likely explanation of this phenomenon lies in the number of PCNA-interacting partners.

Apr 4, 2010 · We propose a novel model in which CRL4 CDT2 -dependent protein degradation facilitates a sequential and dynamic exchange between PIP box-bearing proteins at stall forks during Translesion DNA synthesis (TLS).

Dec 15, 2008 · Interestingly, both the cyclin dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) binding domains of p21 are involved in different aspects of the modulation of TLS, affecting both the interaction between PCNA and the TLS-specific pol eta as well as PCNA ubiquitination status.

Our findings showing that PARP-1 binds both PCNA and p21, and that both interactions increase upon DNA damage, suggest that in vivo PARP-1, PCNA and p21 undergo a dynamic exchange of partners to regulate PCNA functions during DNA replication/repair.

In this study, we have investigated the kinetics of p21 induction by DNA damage and serum stimulation and the consequent effects on cell-cycle progression. Using both normal and repair-deficient human cells, we have also analyzed the nuclear distribution of …

CDK inhibition by p21 triggers cell-cycle arrest in the G1 and G2 phases of the cell cycle. In the absence of exogenous insults causing replication stress, only residual p21 levels are prevalent that are insufficient to inhibit CDKs.

Jun 1, 2016 · P21 phosphorylation in Thr 145 disrupts the hydrogen bond between p21 and PCNA. The released PCNA activates DNA polymerase δ, promotes cell cycle progression during S phase and lead to defect in mismatch repair and base excision repair [14] .

Apr 2, 2019 · Shape-based clustering revealed that the dynamics of the CDK inhibitor p21 diverges from the dynamics of its transcription factor p53 during S phase. Using mathematical modeling, we predict and experimentally validate that S phase-specific degradation of p21 by PCNA-CRL4 cdt2 is sufficient to explain these heterogeneous responses.