BRCA1 downregulates the kinase activity of Polo-like kinase 1 in response to replication stress

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Polo-like kinase-1 in DNA damage response

Polo-like kinase-1 (Plk1) belongs to a family of serine-threonine kinases and plays a critical role in mitotic progression. Plk1 involves in the initiation of mitosis, centrosome maturation, bipolar spindle formation, and cytokinesis, well-reported as traditional functions of Plk1. In this review, we discuss the role of Plk1 during DNA damage response beyond the functions in mitotsis. When DNA ...

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Polo-like kinase 1 inhibits DNA damage response during mitosis

In response to genotoxic stress, cells protect their genome integrity by activation of a conserved DNA damage response (DDR) pathway that coordinates DNA repair and progression through the cell cycle. Extensive modification of the chromatin flanking the DNA lesion by ATM kinase and RNF8/RNF168 ubiquitin ligases enables recruitment of various repair factors. Among them BRCA1 and 53BP1 are requir...

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Polo-like kinase 1 mediates BRCA1 phosphorylation and recruitment at DNA double-strand breaks.

Accurate repair of DNA double-strand breaks (DSB) caused during DNA replication and by exogenous stresses is critical for the maintenance of genomic integrity. There is growing evidence that the Polo-like kinase 1 (Plk1) that plays a number of pivotal roles in cell proliferation can directly participate in regulation of DSB repair. In this study, we show that Plk1 regulates BRCA1, a key mediato...

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Targeting Polo - like Kinase 1 for the Treatment of Cancer

Plk1 levels start to rise significantly at the beginning of S phase, and peak after the G2/M transition [3]. Plk1 plays a critical role in centrosome maturation, kinetochore assembly, and bipolar spindle formation[4]. More importantly, Plk1 plays a key role in ensuring normal mitotic progression. It initiates mitotic entry and mitotic exit by phosphorylating Cyclin B, Cdc25c and by activating t...

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The mitotic roles of Polo-like kinase.

The Polo-like protein kinases (Plks) are a conserved family of enzymes that play a variety of roles in the passage of cells through M phase (for reviews see Glover et al., 1998; Nigg, 1998). Named after the Drosophila polo gene originally identified through a recessive maternal effect lethal mutation, conserved Plk homologues have been identified in yeast, Xenopus, C. elegans and mammals. The i...

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ژورنال

عنوان ژورنال: Cell Cycle

سال: 2013

ISSN: 1538-4101,1551-4005

DOI: 10.4161/cc.25349