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Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding


Asher, G; Reinke, H; Altmeyer, M; Gutierrez-Arcelus, M; Hottiger, M O; Schibler, U (2010). Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell, 142(6):943-953.

Abstract

Circadian clocks in peripheral organs are tightly coupled to cellular metabolism and are readily entrained by feeding-fasting cycles. However, the molecular mechanisms involved are largely unknown. Here we show that in liver the activity of PARP-1, an NAD(+)-dependent ADP-ribosyltransferase, oscillates in a daily manner and is regulated by feeding. We provide biochemical evidence that PARP-1 binds and poly(ADP-ribosyl)ates CLOCK at the beginning of the light phase. The loss of PARP-1 enhances the binding of CLOCK-BMAL1 to DNA and leads to a phase-shift of the interaction of CLOCK-BMAL1 with PER and CRY repressor proteins. As a consequence, CLOCK-BMAL1-dependent gene expression is altered in PARP-1-deficient mice, in particular in response to changes in feeding times. Our results show that Parp-1 knockout mice exhibit impaired food entrainment of peripheral circadian clocks and support a role for PARP-1 in connecting feeding with the mammalian timing system.

Abstract

Circadian clocks in peripheral organs are tightly coupled to cellular metabolism and are readily entrained by feeding-fasting cycles. However, the molecular mechanisms involved are largely unknown. Here we show that in liver the activity of PARP-1, an NAD(+)-dependent ADP-ribosyltransferase, oscillates in a daily manner and is regulated by feeding. We provide biochemical evidence that PARP-1 binds and poly(ADP-ribosyl)ates CLOCK at the beginning of the light phase. The loss of PARP-1 enhances the binding of CLOCK-BMAL1 to DNA and leads to a phase-shift of the interaction of CLOCK-BMAL1 with PER and CRY repressor proteins. As a consequence, CLOCK-BMAL1-dependent gene expression is altered in PARP-1-deficient mice, in particular in response to changes in feeding times. Our results show that Parp-1 knockout mice exhibit impaired food entrainment of peripheral circadian clocks and support a role for PARP-1 in connecting feeding with the mammalian timing system.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease
Dewey Decimal Classification:570 Life sciences; biology
Date:9 September 2010
Deposited On:10 Feb 2011 09:07
Last Modified:05 Apr 2016 14:44
Publisher:Elsevier
ISSN:0092-8674
Publisher DOI:https://doi.org/10.1016/j.cell.2010.08.016
PubMed ID:20832105

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