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

Blank HM, Li C, Mueller JE, Bogomolnaya LM, Bryk M, Polymenis M - PLoS Genet. (2008)

Bottom Line: 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.They also suggest that cellular metabolism may impact on chromatin modifications to regulate the activity of origins of DNA replication.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.

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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Sic1p stability and Abf2p.The levels of galactose-induced Sic1p-TAG were monitored by immunoblotting from cells carrying the indicated plasmids after SIC1-TAG expression was turned off. The signal from Pgk1p was used to estimate loading.
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pgen-1000047-g005: Sic1p stability and Abf2p.The levels of galactose-induced Sic1p-TAG were monitored by immunoblotting from cells carrying the indicated plasmids after SIC1-TAG expression was turned off. The signal from Pgk1p was used to estimate loading.

Mentions: We also examined the levels of the cyclin-dependent kinase (Cdk) inhibitor Sic1p in cells over-expressing Abf2p. In late G1 rising levels of Cdk activity trigger the degradation of Sic1p and initiation of DNA replication [25]. In cells over-expressing Abf2p degradation of Sic1p was initiated sooner than in the control cells (Figure 5), consistent with a shortened G1 phase, but once triggered the rate of Sic1p degradation was unaffected. We obtained identical results in separate repeats of this experiment (Figure S2).


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

Blank HM, Li C, Mueller JE, Bogomolnaya LM, Bryk M, Polymenis M - PLoS Genet. (2008)

Sic1p stability and Abf2p.The levels of galactose-induced Sic1p-TAG were monitored by immunoblotting from cells carrying the indicated plasmids after SIC1-TAG expression was turned off. The signal from Pgk1p was used to estimate loading.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2289842&req=5

pgen-1000047-g005: Sic1p stability and Abf2p.The levels of galactose-induced Sic1p-TAG were monitored by immunoblotting from cells carrying the indicated plasmids after SIC1-TAG expression was turned off. The signal from Pgk1p was used to estimate loading.
Mentions: We also examined the levels of the cyclin-dependent kinase (Cdk) inhibitor Sic1p in cells over-expressing Abf2p. In late G1 rising levels of Cdk activity trigger the degradation of Sic1p and initiation of DNA replication [25]. In cells over-expressing Abf2p degradation of Sic1p was initiated sooner than in the control cells (Figure 5), consistent with a shortened G1 phase, but once triggered the rate of Sic1p degradation was unaffected. We obtained identical results in separate repeats of this experiment (Figure S2).

Bottom Line: 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.They also suggest that cellular metabolism may impact on chromatin modifications to regulate the activity of origins of DNA replication.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, United States of America.

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.

Show MeSH
Related in: MedlinePlus