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Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression.

Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2783-8. Epub 2011 Jan 26
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摘要


The ADP ribosyl transferase [poly(ADP-ribose) polymerase] is a newly characterized member of the family that catalyzes the reaction of ADP ribosylation, a key posttranslational modification of proteins involved in different signaling pathways from DNA damage to energy metabolism and organismal memory. This enzyme shares high structural similarities with the DNA repair enzymes and and accordingly has been found to catalyse poly(ADP ribose) synthesis. However, relatively little is known about its in vivo cellular properties. By combining biochemical studies with the generation and characterization of loss-of-function human and mouse models, we describe as a newcomer in genome integrity and mitotic progression. We report a particular role of Pduanyu373 in cellular response to double-strand breaks, most likely in concert with We identify Pduanyu373 as a critical player in the stabilization of the mitotic spindle and in telomere integrity notably by associating and regulating the mitotic components NuMA and tankyrase 1. Both functions open stimulating prospects for specifically targeting Pduanyu373 in cancer therapy.

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