Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.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.
Bartek,
DNA damage checkpoints: from initiation to recovery or adaptation.
2007, Pubmed
Bartek,
DNA damage checkpoints: from initiation to recovery or adaptation.
2007,
Pubmed
Blow,
Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs.
1986,
Pubmed
,
Xenbase
Byun,
Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint.
2005,
Pubmed
,
Xenbase
Carpenter,
Identification of a novel 81-kDa component of the Xenopus origin recognition complex.
1998,
Pubmed
,
Xenbase
Castro,
Greatwall kinase at a glance.
2018,
Pubmed
Chou,
Protein phosphatase 2A regulates binding of Cdc45 to the prereplication complex.
2002,
Pubmed
,
Xenbase
Costanzo,
An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication.
2003,
Pubmed
,
Xenbase
de Cárcer,
Plk1 overexpression induces chromosomal instability and suppresses tumor development.
2018,
Pubmed
Descombes,
The polo-like kinase Plx1 is required for M phase exit and destruction of mitotic regulators in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Donzelli,
Regulating mammalian checkpoints through Cdc25 inactivation.
2003,
Pubmed
Frank-Vaillant,
Two distinct mechanisms control the accumulation of cyclin B1 and Mos in Xenopus oocytes in response to progesterone.
1999,
Pubmed
,
Xenbase
Ganier,
Metazoan DNA replication origins.
2019,
Pubmed
Gao,
Protein phosphatase 2A and Cdc7 kinase regulate the DNA unwinding element-binding protein in replication initiation.
2014,
Pubmed
,
Xenbase
Goldar,
A dynamic stochastic model for DNA replication initiation in early embryos.
2008,
Pubmed
,
Xenbase
Golsteyn,
Cell cycle regulation of the activity and subcellular localization of Plk1, a human protein kinase implicated in mitotic spindle function.
1995,
Pubmed
Guo,
Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Guo,
Interaction of Chk1 with Treslin negatively regulates the initiation of chromosomal DNA replication.
2015,
Pubmed
,
Xenbase
Hamanaka,
Polo-like kinase is a cell cycle-regulated kinase activated during mitosis.
1995,
Pubmed
Hyrien,
Chromosomal replication initiates and terminates at random sequences but at regular intervals in the ribosomal DNA of Xenopus early embryos.
1993,
Pubmed
,
Xenbase
Jang,
Phosphorylation of threonine 210 and the role of serine 137 in the regulation of mammalian polo-like kinase.
2002,
Pubmed
,
Xenbase
Ji,
Purification and proteomic identification of putative upstream regulators of polo-like kinase-1 from mitotic cell extracts.
2010,
Pubmed
Jin,
SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase.
2003,
Pubmed
Kelm,
Cell cycle-regulated phosphorylation of the Xenopus polo-like kinase Plx1.
2002,
Pubmed
,
Xenbase
Kim,
Dephosphorylation of Plk1 occurs through PP2A-B55/ENSA/Greatwall pathway during mitotic DNA damage recovery.
2019,
Pubmed
Laemmli,
Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
1970,
Pubmed
Lee,
Plk is an M-phase-specific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1.
1995,
Pubmed
Li,
A methylation-phosphorylation switch determines Plk1 kinase activity and function in DNA damage repair.
2019,
Pubmed
Li,
Plk1-dependent phosphorylation regulates functions of DNA topoisomerase IIalpha in cell cycle progression.
2008,
Pubmed
Lindon,
Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells.
2004,
Pubmed
Lopes,
The DNA replication checkpoint response stabilizes stalled replication forks.
2001,
Pubmed
Lu,
Polo-like kinase 1 is essential for early embryonic development and tumor suppression.
2008,
Pubmed
MacDougall,
The structural determinants of checkpoint activation.
2007,
Pubmed
,
Xenbase
Macůrek,
Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery.
2008,
Pubmed
Marheineke,
Aphidicolin triggers a block to replication origin firing in Xenopus egg extracts.
2001,
Pubmed
,
Xenbase
Marheineke,
Control of replication origin density and firing time in Xenopus egg extracts: role of a caffeine-sensitive, ATR-dependent checkpoint.
2004,
Pubmed
,
Xenbase
Maya-Mendoza,
Chk1 regulates the density of active replication origins during the vertebrate S phase.
2007,
Pubmed
McGarry,
Geminin, an inhibitor of DNA replication, is degraded during mitosis.
1998,
Pubmed
,
Xenbase
Michelena,
Basal CHK1 activity safeguards its stability to maintain intrinsic S-phase checkpoint functions.
2019,
Pubmed
Mundt,
On the regulation and function of human polo-like kinase 1 (PLK1): effects of overexpression on cell cycle progression.
1997,
Pubmed
Murphy,
Control of DNA replication by the nucleus/cytoplasm ratio in Xenopus.
2013,
Pubmed
,
Xenbase
Peng,
Repo-man controls a protein phosphatase 1-dependent threshold for DNA damage checkpoint activation.
2010,
Pubmed
,
Xenbase
Platel,
Genome wide decrease of DNA replication eye density at the midblastula transition of Xenopus laevis.
2019,
Pubmed
,
Xenbase
Platel,
Tight Chk1 Levels Control Replication Cluster Activation in Xenopus.
2015,
Pubmed
,
Xenbase
Qian,
Activated polo-like kinase Plx1 is required at multiple points during mitosis in Xenopus laevis.
1998,
Pubmed
,
Xenbase
Qian,
Purification and cloning of a protein kinase that phosphorylates and activates the polo-like kinase Plx1.
1998,
Pubmed
,
Xenbase
Qian,
Mitotic effects of a constitutively active mutant of the Xenopus polo-like kinase Plx1.
1999,
Pubmed
,
Xenbase
Räschle,
Mechanism of replication-coupled DNA interstrand crosslink repair.
2008,
Pubmed
,
Xenbase
Romanowski,
The Xenopus origin recognition complex is essential for DNA replication and MCM binding to chromatin.
1996,
Pubmed
,
Xenbase
Rowles,
Interaction between the origin recognition complex and the replication licensing system in Xenopus.
1996,
Pubmed
,
Xenbase
Santocanale,
A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication.
1998,
Pubmed
Schwab,
ATR activation and replication fork restart are defective in FANCM-deficient cells.
2010,
Pubmed
Seki,
Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry.
2008,
Pubmed
,
Xenbase
Shaltiel,
The same, only different - DNA damage checkpoints and their reversal throughout the cell cycle.
2015,
Pubmed
Shechter,
ATR and ATM regulate the timing of DNA replication origin firing.
2004,
Pubmed
,
Xenbase
Shirahige,
Regulation of DNA-replication origins during cell-cycle progression.
1998,
Pubmed
Sive,
Xenopus laevis In Vitro Fertilization and Natural Mating Methods.
2007,
Pubmed
,
Xenbase
Smith,
Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase.
1997,
Pubmed
Song,
Plk1 phosphorylation of Orc2 promotes DNA replication under conditions of stress.
2011,
Pubmed
Song,
Polo-like kinase 1 (Plk1): an Unexpected Player in DNA Replication.
2012,
Pubmed
Strebhardt,
Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy.
2010,
Pubmed
Sumara,
The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase.
2002,
Pubmed
,
Xenbase
Taniguchi,
Nuclear translocation of plk1 mediated by its bipartite nuclear localization signal.
2002,
Pubmed
Tercero,
Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint.
2001,
Pubmed
Toyoshima,
p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.
1994,
Pubmed
Trenz,
Plx1 is required for chromosomal DNA replication under stressful conditions.
2008,
Pubmed
,
Xenbase
Tsvetkov,
Interaction of chromatin-associated Plk1 and Mcm7.
2005,
Pubmed
Wada,
Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis.
2010,
Pubmed
Wang,
Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α.
2015,
Pubmed
,
Xenbase
Wang,
Protein interactomes of protein phosphatase 2A B55 regulatory subunits reveal B55-mediated regulation of replication protein A under replication stress.
2018,
Pubmed
,
Xenbase
Wen,
SUMOylation Promotes Nuclear Import and Stabilization of Polo-like Kinase 1 to Support Its Mitotic Function.
2017,
Pubmed
Wu,
Role for Plk1 phosphorylation of Hbo1 in regulation of replication licensing.
2008,
Pubmed
Yan,
PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells.
2000,
Pubmed
Yata,
BRCA2 coordinates the activities of cell-cycle kinases to promote genome stability.
2014,
Pubmed
Yim,
Polo-like kinase 1 depletion induces DNA damage in early S prior to caspase activation.
2009,
Pubmed
Yoo,
Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase.
2004,
Pubmed
,
Xenbase
Zeman,
Causes and consequences of replication stress.
2014,
Pubmed
Zhao,
ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1.
2001,
Pubmed
