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Regulation of ribosomal RNA gene copy number and its role in modulating genome integrity and evolutionary adaptability in yeast.

Kobayashi T - Cell. Mol. Life Sci. (2011)

Bottom Line: The unusual nature of rRNA gene repeats affects cellular functions such as senescence.In addition, we recently found that the repeat number determines sensitivity to DNA damage.In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.

View Article: PubMed Central - PubMed

Affiliation: Division of Cytogenetics, National Institute of Genetics/The Graduate University for Advanced Studies, SOKENDAI, 1111 Yata, Mishima, Shizuoka, Japan. takobaya@lab.nig.ac.jp

ABSTRACT
The genes encoding ribosomal RNA (rRNA) are the most abundant genes in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome. A unique gene amplification system compensates for loss of copies, thus maintaining copy number, albeit with some fluctuations. The unusual nature of rRNA gene repeats affects cellular functions such as senescence. In addition, we recently found that the repeat number determines sensitivity to DNA damage. In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.

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Related in: MedlinePlus

rDNA amplification model. a In normal situations, the silencing protein, Sir2, represses E-pro activity, allowing the cohesin protein complex (dotted ellipse) to associate with the IGS. DSBs are repaired by equal sister chromatid recombination, with no change in rDNA copy number. b In situations where copy number is reduced, Sir2 repression is removed and E-pro is activated. This E-pro transcription displaces cohesin from the IGS. The lack of cohesion means that unequal sister chromatids can be used as templates for repair of DSBs, resulting in changes in rDNA copy number. The gray lines represent single chromatids (double-strand DNA) (see text for the details)
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Fig3: rDNA amplification model. a In normal situations, the silencing protein, Sir2, represses E-pro activity, allowing the cohesin protein complex (dotted ellipse) to associate with the IGS. DSBs are repaired by equal sister chromatid recombination, with no change in rDNA copy number. b In situations where copy number is reduced, Sir2 repression is removed and E-pro is activated. This E-pro transcription displaces cohesin from the IGS. The lack of cohesion means that unequal sister chromatids can be used as templates for repair of DSBs, resulting in changes in rDNA copy number. The gray lines represent single chromatids (double-strand DNA) (see text for the details)

Mentions: The gene amplification mechanism that counteracts recombination-mediated loss of rDNA copies is well studied in budding yeast [6, 11]. During the S phase of the cell cycle, replication starts from replication origins, and is inhibited at the replication fork barrier site (RFB) by the function of the fork blocking protein, Fob1 (Fig. 3) [12]. This inhibition works as a recombinational hotspot to induce amplification for copy number recovery as follow; The single-stranded region of the blocked structure may be a target for endonuclease activity, leading to the formation of double-strand breaks. The broken end can then be repaired by homologous recombination with a sister chromatid. In the case of a repetitive sequence like the rDNA, the broken end may also be recombined with a neighboring copy unequally, and re-start replication there. This recombinational repair re-replicates several rDNA copies. As a result, the copy number increases in one of the two sister chromatids.Fig. 3


Regulation of ribosomal RNA gene copy number and its role in modulating genome integrity and evolutionary adaptability in yeast.

Kobayashi T - Cell. Mol. Life Sci. (2011)

rDNA amplification model. a In normal situations, the silencing protein, Sir2, represses E-pro activity, allowing the cohesin protein complex (dotted ellipse) to associate with the IGS. DSBs are repaired by equal sister chromatid recombination, with no change in rDNA copy number. b In situations where copy number is reduced, Sir2 repression is removed and E-pro is activated. This E-pro transcription displaces cohesin from the IGS. The lack of cohesion means that unequal sister chromatids can be used as templates for repair of DSBs, resulting in changes in rDNA copy number. The gray lines represent single chromatids (double-strand DNA) (see text for the details)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3064901&req=5

Fig3: rDNA amplification model. a In normal situations, the silencing protein, Sir2, represses E-pro activity, allowing the cohesin protein complex (dotted ellipse) to associate with the IGS. DSBs are repaired by equal sister chromatid recombination, with no change in rDNA copy number. b In situations where copy number is reduced, Sir2 repression is removed and E-pro is activated. This E-pro transcription displaces cohesin from the IGS. The lack of cohesion means that unequal sister chromatids can be used as templates for repair of DSBs, resulting in changes in rDNA copy number. The gray lines represent single chromatids (double-strand DNA) (see text for the details)
Mentions: The gene amplification mechanism that counteracts recombination-mediated loss of rDNA copies is well studied in budding yeast [6, 11]. During the S phase of the cell cycle, replication starts from replication origins, and is inhibited at the replication fork barrier site (RFB) by the function of the fork blocking protein, Fob1 (Fig. 3) [12]. This inhibition works as a recombinational hotspot to induce amplification for copy number recovery as follow; The single-stranded region of the blocked structure may be a target for endonuclease activity, leading to the formation of double-strand breaks. The broken end can then be repaired by homologous recombination with a sister chromatid. In the case of a repetitive sequence like the rDNA, the broken end may also be recombined with a neighboring copy unequally, and re-start replication there. This recombinational repair re-replicates several rDNA copies. As a result, the copy number increases in one of the two sister chromatids.Fig. 3

Bottom Line: The unusual nature of rRNA gene repeats affects cellular functions such as senescence.In addition, we recently found that the repeat number determines sensitivity to DNA damage.In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.

View Article: PubMed Central - PubMed

Affiliation: Division of Cytogenetics, National Institute of Genetics/The Graduate University for Advanced Studies, SOKENDAI, 1111 Yata, Mishima, Shizuoka, Japan. takobaya@lab.nig.ac.jp

ABSTRACT
The genes encoding ribosomal RNA (rRNA) are the most abundant genes in the eukaryotic genome. They reside in tandem repetitive clusters, in some cases totaling hundreds of copies. Due to their repetitive structure and highly active transcription, the rRNA gene repeats are some of the most fragile sites in the chromosome. A unique gene amplification system compensates for loss of copies, thus maintaining copy number, albeit with some fluctuations. The unusual nature of rRNA gene repeats affects cellular functions such as senescence. In addition, we recently found that the repeat number determines sensitivity to DNA damage. In this review, I would like to introduce a new aspect of the rRNA gene repeat (called rDNA) as a center of maintenance of genome integrity and discuss its contribution to evolution.

Show MeSH
Related in: MedlinePlus