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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

ROS mediated double-stranded breakage at the mtDNA replication origin, ori5.
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f4-genes-02-00169: ROS mediated double-stranded breakage at the mtDNA replication origin, ori5.

Mentions: Since single-stranded DNA is much more sensitive to damaging agents, including ROS, than double-stranded DNA, the local single-stranded nature and the enzymatic specificities of Ntg1 explain the locus-specific oxidation of bases and the double-stranded breakage at ori5 [62] (Figure 4). Thus, ROS act as signal mediators to regulate mtDNA replication and copy number [62].


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

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

ROS mediated double-stranded breakage at the mtDNA replication origin, ori5.
© Copyright Policy
Related In: Results  -  Collection

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

f4-genes-02-00169: ROS mediated double-stranded breakage at the mtDNA replication origin, ori5.
Mentions: Since single-stranded DNA is much more sensitive to damaging agents, including ROS, than double-stranded DNA, the local single-stranded nature and the enzymatic specificities of Ntg1 explain the locus-specific oxidation of bases and the double-stranded breakage at ori5 [62] (Figure 4). Thus, ROS act as signal mediators to regulate mtDNA replication and copy number [62].

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