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Enlightenment of yeast mitochondrial homoplasmy: diversified roles of gene conversion.

Ling F, Mikawa T, Shibata T - Genes (Basel) (2011)

Bottom Line: Gene conversion generates sequence diversity, depending on the divergence between the donor and recipient sequences, especially when it occurs among a number of copies of a DNA sequence family with some sequence variations, such as in immunoglobulin diversification in chicken.Thus, it would be interesting to determine why and how double-stranded breakage and D-loop formation induce sequence homogenization in mitochondria and sequence diversification in nuclear DNA.We will review the mechanisms and roles of mtDNA homoplasmy, in contrast to nuclear gene conversion, which diversifies gene and genome sequences, to provide clues toward understanding how the common DNA processing pathway results in such divergent outcomes.

View Article: PubMed Central - PubMed

Affiliation: Chemical Genetics Laboratory, RIKEN Advanced Science Institute/2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. ling@postman.riken.go.jp.

ABSTRACT
Mitochondria have their own genomic DNA. Unlike the nuclear genome, each cell contains hundreds to thousands of copies of mitochondrial DNA (mtDNA). The copies of mtDNA tend to have heterogeneous sequences, due to the high frequency of mutagenesis, but are quickly homogenized within a cell ("homoplasmy") during vegetative cell growth or through a few sexual generations. Heteroplasmy is strongly associated with mitochondrial diseases, diabetes and aging. Recent studies revealed that the yeast cell has the machinery to homogenize mtDNA, using a common DNA processing pathway with gene conversion; i.e., both genetic events are initiated by a double-stranded break, which is processed into 3' single-stranded tails. One of the tails is base-paired with the complementary sequence of the recipient double-stranded DNA to form a D-loop (homologous pairing), in which repair DNA synthesis is initiated to restore the sequence lost by the breakage. Gene conversion generates sequence diversity, depending on the divergence between the donor and recipient sequences, especially when it occurs among a number of copies of a DNA sequence family with some sequence variations, such as in immunoglobulin diversification in chicken. MtDNA can be regarded as a sequence family, in which the members tend to be diversified by a high frequency of spontaneous mutagenesis. Thus, it would be interesting to determine why and how double-stranded breakage and D-loop formation induce sequence homogenization in mitochondria and sequence diversification in nuclear DNA. We will review the mechanisms and roles of mtDNA homoplasmy, in contrast to nuclear gene conversion, which diversifies gene and genome sequences, to provide clues toward understanding how the common DNA processing pathway results in such divergent outcomes.

No MeSH data available.


Related in: MedlinePlus

Mechanism for the efficient segregation of heteroplasmic cells in the yeast, S. cerevisiae. In the heteroplasmic mother cell, a randomly selected template circular DNA molecule (a blue circle in “Mother cell”) is replicated in a rolling circle mode to produce concatemers. The concatemers are selectively transmitted to daughter cells by a mechanism resembling that of terminases, which are ATP-dependent motor proteins that package a single phage genome unit from the phage DNA concatemers into the phage capsid [54]. Upon transmission into the daughter cells, the concatemers are processed into circular monomers (blue circles in “Daughter cell”), as in the case of phage DNA packaging [12] and constitute homoplasmic mtDNA.
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f3-genes-02-00169: Mechanism for the efficient segregation of heteroplasmic cells in the yeast, S. cerevisiae. In the heteroplasmic mother cell, a randomly selected template circular DNA molecule (a blue circle in “Mother cell”) is replicated in a rolling circle mode to produce concatemers. The concatemers are selectively transmitted to daughter cells by a mechanism resembling that of terminases, which are ATP-dependent motor proteins that package a single phage genome unit from the phage DNA concatemers into the phage capsid [54]. Upon transmission into the daughter cells, the concatemers are processed into circular monomers (blue circles in “Daughter cell”), as in the case of phage DNA packaging [12] and constitute homoplasmic mtDNA.

Mentions: The mechanistic roles of Mhr1 in mtDNA partitioning into daughter cells were revealed when the ρ+ mtDNA (ca. 80 kbp) was analyzed in mother cells and growing buds separated from dividing cells, by the use of pulsed-field gel electrophoresis. The major species of mtDNA in the mother cells was multimers, as observed in whole cells, but in the bud, the major mtDNA species was monomers [12]. Detailed information about the forms of mtDNA in the mother and daughter cells was obtained by the analysis of small ρ− mtDNA (ca. 10 kbp) by 1D and 2D agarose gel-electrophoresis. The major species of mtDNA in cells are linear head-to-tail multimers of varying sizes (concatemers) in the mother cells, and circular monomers in daughter cells [12,13]. The amounts of ρ− mtDNA concatemers depend on the activity of Mhr1 within cells, as revealed by the effects of mhr1-1 and the overexpression of Mhr1 in yeast cells [13]. These features are very similar to those observed in the late phase of DNA replication and packaging of E. coli phages lambda and E. coli phage T4 DNA replication; i.e., recombination-dependent formation of concatemers, and selective packing of concatemers into phage capsids by terminase [31,53]. The defective partitioning of mtDNA in mhr1-1 yeast cells indicates that the concatemers formed by Mhr1-dependent mtDNA replication are an essential intermediate for partitioning promoted by the terminase-like enzyme (Figure 3).


Enlightenment of yeast mitochondrial homoplasmy: diversified roles of gene conversion.

Ling F, Mikawa T, Shibata T - Genes (Basel) (2011)

Mechanism for the efficient segregation of heteroplasmic cells in the yeast, S. cerevisiae. In the heteroplasmic mother cell, a randomly selected template circular DNA molecule (a blue circle in “Mother cell”) is replicated in a rolling circle mode to produce concatemers. The concatemers are selectively transmitted to daughter cells by a mechanism resembling that of terminases, which are ATP-dependent motor proteins that package a single phage genome unit from the phage DNA concatemers into the phage capsid [54]. Upon transmission into the daughter cells, the concatemers are processed into circular monomers (blue circles in “Daughter cell”), as in the case of phage DNA packaging [12] and constitute homoplasmic mtDNA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924846&req=5

f3-genes-02-00169: Mechanism for the efficient segregation of heteroplasmic cells in the yeast, S. cerevisiae. In the heteroplasmic mother cell, a randomly selected template circular DNA molecule (a blue circle in “Mother cell”) is replicated in a rolling circle mode to produce concatemers. The concatemers are selectively transmitted to daughter cells by a mechanism resembling that of terminases, which are ATP-dependent motor proteins that package a single phage genome unit from the phage DNA concatemers into the phage capsid [54]. Upon transmission into the daughter cells, the concatemers are processed into circular monomers (blue circles in “Daughter cell”), as in the case of phage DNA packaging [12] and constitute homoplasmic mtDNA.
Mentions: The mechanistic roles of Mhr1 in mtDNA partitioning into daughter cells were revealed when the ρ+ mtDNA (ca. 80 kbp) was analyzed in mother cells and growing buds separated from dividing cells, by the use of pulsed-field gel electrophoresis. The major species of mtDNA in the mother cells was multimers, as observed in whole cells, but in the bud, the major mtDNA species was monomers [12]. Detailed information about the forms of mtDNA in the mother and daughter cells was obtained by the analysis of small ρ− mtDNA (ca. 10 kbp) by 1D and 2D agarose gel-electrophoresis. The major species of mtDNA in cells are linear head-to-tail multimers of varying sizes (concatemers) in the mother cells, and circular monomers in daughter cells [12,13]. The amounts of ρ− mtDNA concatemers depend on the activity of Mhr1 within cells, as revealed by the effects of mhr1-1 and the overexpression of Mhr1 in yeast cells [13]. These features are very similar to those observed in the late phase of DNA replication and packaging of E. coli phages lambda and E. coli phage T4 DNA replication; i.e., recombination-dependent formation of concatemers, and selective packing of concatemers into phage capsids by terminase [31,53]. The defective partitioning of mtDNA in mhr1-1 yeast cells indicates that the concatemers formed by Mhr1-dependent mtDNA replication are an essential intermediate for partitioning promoted by the terminase-like enzyme (Figure 3).

Bottom Line: Gene conversion generates sequence diversity, depending on the divergence between the donor and recipient sequences, especially when it occurs among a number of copies of a DNA sequence family with some sequence variations, such as in immunoglobulin diversification in chicken.Thus, it would be interesting to determine why and how double-stranded breakage and D-loop formation induce sequence homogenization in mitochondria and sequence diversification in nuclear DNA.We will review the mechanisms and roles of mtDNA homoplasmy, in contrast to nuclear gene conversion, which diversifies gene and genome sequences, to provide clues toward understanding how the common DNA processing pathway results in such divergent outcomes.

View Article: PubMed Central - PubMed

Affiliation: Chemical Genetics Laboratory, RIKEN Advanced Science Institute/2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. ling@postman.riken.go.jp.

ABSTRACT
Mitochondria have their own genomic DNA. Unlike the nuclear genome, each cell contains hundreds to thousands of copies of mitochondrial DNA (mtDNA). The copies of mtDNA tend to have heterogeneous sequences, due to the high frequency of mutagenesis, but are quickly homogenized within a cell ("homoplasmy") during vegetative cell growth or through a few sexual generations. Heteroplasmy is strongly associated with mitochondrial diseases, diabetes and aging. Recent studies revealed that the yeast cell has the machinery to homogenize mtDNA, using a common DNA processing pathway with gene conversion; i.e., both genetic events are initiated by a double-stranded break, which is processed into 3' single-stranded tails. One of the tails is base-paired with the complementary sequence of the recipient double-stranded DNA to form a D-loop (homologous pairing), in which repair DNA synthesis is initiated to restore the sequence lost by the breakage. Gene conversion generates sequence diversity, depending on the divergence between the donor and recipient sequences, especially when it occurs among a number of copies of a DNA sequence family with some sequence variations, such as in immunoglobulin diversification in chicken. MtDNA can be regarded as a sequence family, in which the members tend to be diversified by a high frequency of spontaneous mutagenesis. Thus, it would be interesting to determine why and how double-stranded breakage and D-loop formation induce sequence homogenization in mitochondria and sequence diversification in nuclear DNA. We will review the mechanisms and roles of mtDNA homoplasmy, in contrast to nuclear gene conversion, which diversifies gene and genome sequences, to provide clues toward understanding how the common DNA processing pathway results in such divergent outcomes.

No MeSH data available.


Related in: MedlinePlus