An increase in mitochondrial DNA promotes nuclear DNA replication in yeast.

PLoS Genetics
Heidi M BlankMichael Polymenis

Abstract

Coordination between cellular metabolism and DNA replication determines when cells initiate division. It has been assumed that metabolism only plays a permissive role in cell division. While blocking metabolism arrests cell division, it is not known whether an up-regulation of metabolic reactions accelerates cell cycle transitions. Here, we show that increasing the amount of mitochondrial DNA accelerates overall cell proliferation and promotes nuclear DNA replication, in a nutrient-dependent manner. The Sir2p NAD+-dependent de-acetylase antagonizes this mitochondrial role. We found that cells with increased mitochondrial DNA have reduced Sir2p levels bound at origins of DNA replication in the nucleus, accompanied with increased levels of K9, K14-acetylated histone H3 at those origins. Our results demonstrate an active role of mitochondrial processes in the control of cell division. They also suggest that cellular metabolism may impact on chromatin modifications to regulate the activity of origins of DNA replication.

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Citations

Dec 4, 2009·PloS One·Heidi M BlankMichael Polymenis
Feb 22, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Raymond G FoxNobuyo Maeda
Dec 17, 2014·Nutrients·Justin M O'SullivanJulia A Horsfield
Jul 25, 2009·Fungal Genetics and Biology : FG & B·C D M RodleyJ M O'Sullivan
Jan 22, 2010·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·John Herrick
Jun 12, 2012·Journal of Structural Biology·L'uboš AmbroEva Kutejová
May 10, 2015·Medical Hypotheses·Yucai ChenKunfang Yang
Apr 16, 2010·Current Opinion in Cell Biology·Justin M O'Sullivan

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Methods Mentioned

BETA
histone acetylation
acetylation
flow cytometry
PCR
ChIP
immunoprecipitation
electrophoresis
immunoprecipitations

Software Mentioned

Adobe Photoshop
Imagequant
Quantity One
Adobe Photoshop®
Excel
ModFit®

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