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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

mtDNA is required for the accelerated DNA replication in 3xABF2+ cells.A, Cell cycle progression of elutriated cells was analyzed exactly as in Figure 4, except that the strains used were made ρ− as described in the Methods. B, Loss of SIR2 accelerates DNA replication in the S288C strain background. The elutriation experiment was done as in Figure 4, except that the strains used were in a different strain background, described previously [14].
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pgen-1000047-g006: mtDNA is required for the accelerated DNA replication in 3xABF2+ cells.A, Cell cycle progression of elutriated cells was analyzed exactly as in Figure 4, except that the strains used were made ρ− as described in the Methods. B, Loss of SIR2 accelerates DNA replication in the S288C strain background. The elutriation experiment was done as in Figure 4, except that the strains used were in a different strain background, described previously [14].

Mentions: We next generated the corresponding ρ− strains to test whether over-expression of ABF2+ requires mtDNA to promote DNA replication. These strains are respiratory incompetent (Figure S4A). DNA replication was not accelerated in 3xABF2+ (ρ−) cells (Figure 6A). Overall, in contrast to ρ+ cells (see Figure 4 and Figure S1) the critical budding size (Figure S4B), and the rate of cell size increase after elutriation (Figure S4C), were not significantly different between ABF2+ (ρ−) and 3xABF2+ (ρ−) cells: P = 0.43, and P = 0.54, respectively (based on 2-tailed Student's t tests). In conclusion, our findings suggest that altered mitochondrial functions in 3xABF2+ cells impact on some factor(s) that affect DNA replication.


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)

mtDNA is required for the accelerated DNA replication in 3xABF2+ cells.A, Cell cycle progression of elutriated cells was analyzed exactly as in Figure 4, except that the strains used were made ρ− as described in the Methods. B, Loss of SIR2 accelerates DNA replication in the S288C strain background. The elutriation experiment was done as in Figure 4, except that the strains used were in a different strain background, described previously [14].
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1000047-g006: mtDNA is required for the accelerated DNA replication in 3xABF2+ cells.A, Cell cycle progression of elutriated cells was analyzed exactly as in Figure 4, except that the strains used were made ρ− as described in the Methods. B, Loss of SIR2 accelerates DNA replication in the S288C strain background. The elutriation experiment was done as in Figure 4, except that the strains used were in a different strain background, described previously [14].
Mentions: We next generated the corresponding ρ− strains to test whether over-expression of ABF2+ requires mtDNA to promote DNA replication. These strains are respiratory incompetent (Figure S4A). DNA replication was not accelerated in 3xABF2+ (ρ−) cells (Figure 6A). Overall, in contrast to ρ+ cells (see Figure 4 and Figure S1) the critical budding size (Figure S4B), and the rate of cell size increase after elutriation (Figure S4C), were not significantly different between ABF2+ (ρ−) and 3xABF2+ (ρ−) cells: P = 0.43, and P = 0.54, respectively (based on 2-tailed Student's t tests). In conclusion, our findings suggest that altered mitochondrial functions in 3xABF2+ cells impact on some factor(s) that affect DNA replication.

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