Polo-like kinase 1 (Plk1) is a positive regulator of DNA replication in the Xenopus in vitro system.
Cell Cycle
; 19(14): 1817-1832, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32573322
ABSTRACT
Polo-like kinase 1 (Plk1) is a cell cycle kinase essential for mitosis progression, but also important for checkpoint recovery and adaptation in response to DNA damage and replication stress. However, although Plk1 is expressed in S phase, little is known about its function during unperturbed DNA replication. Using Xenopus laevis egg extracts, mimicking early embryonic replication, we demonstrate that Plk1 is simultaneously recruited to chromatin with pre-replication proteins where it accumulates throughout S phase. Further, we found that chromatin-bound Plk1 is phosphorylated on its activating site T201, which appears to be sensitive to dephosphorylation by protein phosphatase 2A. Extracts immunodepleted of Plk1 showed a decrease in DNA replication, rescued by wild type recombinant Plk1. Inversely, modest Plk1 overexpression accelerated DNA replication. Plk1 depletion led to an increase in Chk1 phosphorylation and to a decrease in Cdk2 activity, which strongly suggests that Plk1 could inhibit the ATR/Chk1-dependent intra-S phase checkpoint during normal S phase. In addition, we observed that phosphorylated Plk1 levels are high during the rapid, early cell cycles of Xenopus development but decrease after the mid-blastula transition when the cell cycle and the replication program slow down along with more active checkpoints. These data shed new light on the role of Plk1 as a positive regulating factor for DNA replication in early, rapidly dividing embryos.
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MEDLINE
Assunto principal:
Xenopus laevis
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Proteínas Proto-Oncogênicas
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Proteínas Serina-Treonina Quinases
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Proteínas de Ciclo Celular
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Replicação do DNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article