Polo-like kinase 1 (Plk1) regulates DNA replication origin firing and interacts with Rif1 in <i>Xenopus</i>

Ciardo, Diletta; Haccard, Olivier; Narassimprakash, Hemalatha; Cornu, David; Guerrera, Ida Chiara; Goldar, Arach; Marheineke, Kathrin

doi:10.1093/nar/gkab756

Cited by 16 publications

(38 citation statements)

References 80 publications

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“…Recently, PLK1 was shown in an in vitro system to be essential in regulating the spatio-temporal replication program by interacting with several origin firing factors (i.e. RIF1, TRESLIN; TopBP1), and the immuno-depletion of PLK1 reduced the number of replication forks and origins firing ( 35 ), giving additional proof of the PLK1’s role also in S-phase.…”

Section: Plk1 and Its Role In Genomic Stabilitymentioning

confidence: 99%

Present and Future Perspective on PLK1 Inhibition in Cancer Treatment

Chiappa

Petrella²,

Damia³

et al. 2022

Front. Oncol.

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Polo-like kinase 1 (PLK1) is the principle member of the well conserved serine/threonine kinase family. PLK1 has a key role in the progression of mitosis and recent evidence suggest its important involvement in regulating the G2/M checkpoint, in DNA damage and replication stress response, and in cell death pathways. PLK1 expression is tightly spatially and temporally regulated to ensure its nuclear activation at the late S-phase, until the peak of expression at the G2/M-phase. Recently, new roles of PLK1 have been reported in literature on its implication in the regulation of inflammation and immunological responses. All these biological processes are altered in tumors and, considering that PLK1 is often found overexpressed in several tumor types, its targeting has emerged as a promising anti-cancer therapeutic strategy. In this review, we will summarize the evidence suggesting the role of PLK1 in response to DNA damage, including DNA repair, cell cycle progression, epithelial to mesenchymal transition, cell death pathways and cancer-related immunity. An update of PLK1 inhibitors currently investigated in preclinical and clinical studies, in monotherapy and in combination with existing chemotherapeutic drugs and targeted therapies will be discussed.

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Section: Plk1 and Its Role In Genomic Stabilitymentioning

confidence: 99%

Present and Future Perspective on PLK1 Inhibition in Cancer Treatment

Chiappa

Petrella²,

Damia³

et al. 2022

Front. Oncol.

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“…In human cells, Rif1-phosphorylation is also dependent on CDK1 [ 69 ]. In Xenopus egg extract, which mimics the first S phase after fertilization, depletion of Rif1 or Rif1-CTD (C-terminal domain that contains PP1-binding site) results in less PP1 on chromatin and a reduced rate of MCM-phosphorylation [ 69 , 70 ]. This suggests that Rif1 has the potential to regulate replication in the earliest stages of vertebrate development.…”

Section: Rif1 Activity Is Regulated During Developmentmentioning

confidence: 99%

“…This suggests that Rif1 has the potential to regulate replication in the earliest stages of vertebrate development. Interestingly, in Xenopus, Polo-like kinase 1 (Plk1) can phosphorylate Rif1 near its PP1-binding site, suggesting that Rif1 is the target of multiple cell-cycle-regulated kinases [ 70 ].…”

Section: Rif1 Activity Is Regulated During Developmentmentioning

confidence: 99%

Rif1-Dependent Control of Replication Timing

Richards

Das

Nordman

2022

Genes

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Successful duplication of the genome requires the accurate replication of billions of base pairs of DNA within a relatively short time frame. Failure to accurately replicate the genome results in genomic instability and a host of diseases. To faithfully and rapidly replicate the genome, DNA replication must be tightly regulated and coordinated with many other nuclear processes. These regulations, however, must also be flexible as replication kinetics can change through development and differentiation. Exactly how DNA replication is regulated and how this regulation changes through development is an active field of research. One aspect of genome duplication where much remains to be discovered is replication timing (RT), which dictates when each segment of the genome is replicated during S phase. All organisms display some level of RT, yet the precise mechanisms that govern RT remain are not fully understood. The study of Rif1, a protein that actively regulates RT from yeast to humans, provides a key to unlock the underlying molecular mechanisms controlling RT. The paradigm for Rif1 function is to delay helicase activation within certain regions of the genome, causing these regions to replicate late in S phase. Many questions, however, remain about the intricacies of Rif1 function. Here, we review the current models for the activity of Rif1 with the goal of trying to understand how Rif1 functions to establish the RT program.

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“…Independently of MCM phosphorylation, DDK activity has been shown to promote the formation of Treslin:MTBP:TopBP1 complex that supports replication initiation ( Figure 2 iv,v). The DDK substrate mediating this increased complex formation remains to be fully characterised as both Treslin and MTBP demonstrate a DDK-dependent mobility shift [ 5 , 70 ]. Furthermore, it was shown that DDK-dependent phosphorylation of Treslin is required to facilitate the conserved CDK-mediated phosphorylation of Treslin that is required for interaction with TopBP1 [ 5 ].…”

Section: Replication Origin Selection and Activation: Ddk-mediated Ph...mentioning

confidence: 99%

DDK: The Outsourced Kinase of Chromosome Maintenance

Gillespie

Blow

2022

Biology

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The maintenance of genomic stability during the mitotic cell-cycle not only demands that the DNA is duplicated and repaired with high fidelity, but that following DNA replication the chromatin composition is perpetuated and that the duplicated chromatids remain tethered until their anaphase segregation. The coordination of these processes during S phase is achieved by both cyclin-dependent kinase, CDK, and Dbf4-dependent kinase, DDK. CDK orchestrates the activation of DDK at the G1-to-S transition, acting as the ‘global’ regulator of S phase and cell-cycle progression, whilst ‘local’ control of the initiation of DNA replication and repair and their coordination with the re-formation of local chromatin environments and the establishment of chromatid cohesion are delegated to DDK. Here, we discuss the regulation and the multiple roles of DDK in ensuring chromosome maintenance. Regulation of replication initiation by DDK has long been known to involve phosphorylation of MCM2-7 subunits, but more recent results have indicated that Treslin:MTBP might also be important substrates. Molecular mechanisms by which DDK regulates replisome stability and replicated chromatid cohesion are less well understood, though important new insights have been reported recently. We discuss how the ‘outsourcing’ of activities required for chromosome maintenance to DDK allows CDK to maintain outright control of S phase progression and the cell-cycle phase transitions whilst permitting ongoing chromatin replication and cohesion establishment to be completed and achieved faithfully.

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Polo-like kinase 1 (Plk1) regulates DNA replication origin firing and interacts with Rif1 in Xenopus

Cited by 16 publications

References 80 publications

Present and Future Perspective on PLK1 Inhibition in Cancer Treatment

Present and Future Perspective on PLK1 Inhibition in Cancer Treatment

Rif1-Dependent Control of Replication Timing

DDK: The Outsourced Kinase of Chromosome Maintenance

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