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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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Related in: MedlinePlus

Over-expression of ABF2, or loss of SIR2, accelerates DNA replication.Synchronous cultures of the indicated strains were obtained by centrifugal elutriation and the starting populations of each strain were of the same size. At the indicated times the DNA content was evaluated by flow cytometry.
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pgen-1000047-g004: Over-expression of ABF2, or loss of SIR2, accelerates DNA replication.Synchronous cultures of the indicated strains were obtained by centrifugal elutriation and the starting populations of each strain were of the same size. At the indicated times the DNA content was evaluated by flow cytometry.

Mentions: Because 3xABF2+ populations proliferate faster (Figure 1A) and have a reduced fraction of G1 cells (Figure 1B), we hypothesized that DNA replication may be accelerated in 3xABF2+ cells. We examined cell cycle progression of ABF2+ and 3xABF2+ cells from synchronous cultures obtained by centrifugal elutriation. We used standard [24] undefined medium (YPD) for these experiments, with lower glucose concentration (0.5%). A higher fraction of 3xABF2+ cells entered S phase sooner than ABF2+ cells (Figure 4, compare the top two rows). For example, at 60 min post-elutriation of ABF2+ cells 10.7% were budded and 46.2% in G1, while of 3xABF2+ cells 40.2% were budded and 32% were in G1. In addition, the 3xABF2+ cells completed S phase sooner than ABF2+ cells (see Figure 4 compare the top two rows): At 80 min post elutriation, note the size of the G2/M peak relative to the G1 peak. More 3xABF2+ cells have completed DNA replication than ABF2+ cells. Finally, although in asynchronous populations the overall cell size of 3xABF2+ cells was not different from ABF2+ cells (Figure 2A), the elutriated daughter 3xABF2+ G1 cells increased in size faster than their ABF2+ counterparts (Figure 4, compare the top two rows): at 60 min 3xABF2+ cells are 40.2 fl, while ABF2+ cells are 37.1 fl, consistent with a growth-promoting role of Abf2p.


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)

Over-expression of ABF2, or loss of SIR2, accelerates DNA replication.Synchronous cultures of the indicated strains were obtained by centrifugal elutriation and the starting populations of each strain were of the same size. At the indicated times the DNA content was evaluated by flow cytometry.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1000047-g004: Over-expression of ABF2, or loss of SIR2, accelerates DNA replication.Synchronous cultures of the indicated strains were obtained by centrifugal elutriation and the starting populations of each strain were of the same size. At the indicated times the DNA content was evaluated by flow cytometry.
Mentions: Because 3xABF2+ populations proliferate faster (Figure 1A) and have a reduced fraction of G1 cells (Figure 1B), we hypothesized that DNA replication may be accelerated in 3xABF2+ cells. We examined cell cycle progression of ABF2+ and 3xABF2+ cells from synchronous cultures obtained by centrifugal elutriation. We used standard [24] undefined medium (YPD) for these experiments, with lower glucose concentration (0.5%). A higher fraction of 3xABF2+ cells entered S phase sooner than ABF2+ cells (Figure 4, compare the top two rows). For example, at 60 min post-elutriation of ABF2+ cells 10.7% were budded and 46.2% in G1, while of 3xABF2+ cells 40.2% were budded and 32% were in G1. In addition, the 3xABF2+ cells completed S phase sooner than ABF2+ cells (see Figure 4 compare the top two rows): At 80 min post elutriation, note the size of the G2/M peak relative to the G1 peak. More 3xABF2+ cells have completed DNA replication than ABF2+ cells. Finally, although in asynchronous populations the overall cell size of 3xABF2+ cells was not different from ABF2+ cells (Figure 2A), the elutriated daughter 3xABF2+ G1 cells increased in size faster than their ABF2+ counterparts (Figure 4, compare the top two rows): at 60 min 3xABF2+ cells are 40.2 fl, while ABF2+ cells are 37.1 fl, consistent with a growth-promoting role of Abf2p.

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