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Regulation of Poly(ADP-Ribose) Polymerase 1 Activity by Y-Box-Binding Protein 1

Abstract : Y-box-binding protein 1 (YB-1) is a multifunctional positively charged protein that interacts with DNA or RNA and poly(ADP-ribose) (PAR). YB-1 is poly(ADP-ribosyl)ated and stimulates poly(ADP-ribose) polymerase 1 (PARP1) activity. Here, we studied the mechanism of YB-1-dependent PAR synthesis by PARP1 in vitro using biochemical and atomic force microscopy assays. PAR synthesis activity of PARP1 is known to be facilitated by co-factors such as Mg2+. However, in contrast to an Mg2+-dependent reaction, the activation of PARP1 by YB-1 is accompanied by overall up-regulation of protein PARylation and shortening of the PAR polymer. Therefore, YB-1 and cation co-factors stimulated PAR synthesis in divergent ways. PARP1 autoPARylation in the presence of YB-1 as well as trans-PARylation of YB-1 are greatly a ected by the type of damaged DNA, suggesting that PARP1 activation depends on the formation of a PARP1–YB-1–DNA ternary complex. An unstructured C-terminal part of YB-1 involved in an interaction with PAR behaves similarly to full-length YB-1, indicating that both DNA and PAR binding are involved in the stimulation of PARP1 activity by YB-1. Thus, YB-1 is likely linked to the regulation of PARylation events in cells via an interaction with PAR and damaged DNA.
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https://hal-univ-evry.archives-ouvertes.fr/hal-02968966
Contributor : Olek Maciejak <>
Submitted on : Friday, October 16, 2020 - 11:31:54 AM
Last modification on : Thursday, October 22, 2020 - 9:50:37 AM

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Konstantin Naumenko, Mariya Sukhanova, Loic Hamon, Tatyana Kurgina, Elizaveta Alemasova, et al.. Regulation of Poly(ADP-Ribose) Polymerase 1 Activity by Y-Box-Binding Protein 1. Biomolecules, MDPI, 2020, 10 (9), pp.1325. ⟨10.3390/biom10091325⟩. ⟨hal-02968966⟩

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