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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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Loss of Sir2p does not accelerate overall cell proliferation.Chemostat competition experiments between SIR2+ and sir2Δ cells (in the 14ww strain background) were done during glucose limitation at dilution rate D = 0.1 h−1, as described in Figure 1.
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pgen-1000047-g008: Loss of Sir2p does not accelerate overall cell proliferation.Chemostat competition experiments between SIR2+ and sir2Δ cells (in the 14ww strain background) were done during glucose limitation at dilution rate D = 0.1 h−1, as described in Figure 1.

Mentions: We next asked if Sir2p negatively affects cellular metabolism to delay DNA replication. We found that sir2Δ cells did not proliferate faster than SIR2+ cells under glucose limitation in chemostats (Figure 8). Thus, loss of Sir2p does not up-regulate metabolic functions necessary to achieve the proliferation advantage evident in 3xABF2+ cells under the same conditions (Figure 1A).


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)

Loss of Sir2p does not accelerate overall cell proliferation.Chemostat competition experiments between SIR2+ and sir2Δ cells (in the 14ww strain background) were done during glucose limitation at dilution rate D = 0.1 h−1, as described in Figure 1.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1000047-g008: Loss of Sir2p does not accelerate overall cell proliferation.Chemostat competition experiments between SIR2+ and sir2Δ cells (in the 14ww strain background) were done during glucose limitation at dilution rate D = 0.1 h−1, as described in Figure 1.
Mentions: We next asked if Sir2p negatively affects cellular metabolism to delay DNA replication. We found that sir2Δ cells did not proliferate faster than SIR2+ cells under glucose limitation in chemostats (Figure 8). Thus, loss of Sir2p does not up-regulate metabolic functions necessary to achieve the proliferation advantage evident in 3xABF2+ cells under the same conditions (Figure 1A).

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