Abundance of ribosomal RNA gene copies maintains genome integrity.
The ribosomal RNA (rDNA) gene repeats are essential housekeeping genes found in all organisms. A gene amplification system maintains large cluster(s) of tandemly repeated copies in the chromosome, with each species having a specific number of copies. Yeast has many untranscribed rDNA copies (extra copies), and we found that when they are lost, the cells become sensitive to DNA damage induced by mutagens. We show that this sensitivity is dependent on rDNA transcriptional activity, which interferes with cohesion between rDNA loci of sister chromatids. The extra rDNA copies facilitate condensin association and sister-chromatid cohesion, thereby facilitating recombinational repair. These results suggest that high concentrations of heavily transcribed genes are toxic to the cells, and therefore amplified genes, such as rDNA, have evolved.
Ide
Satoru
S
National Institute of Genetics, Sokendai, 1111 Yata, Mishima, 411-8540 Japan.
Miyazaki
Takaaki
T
Maki
Hisaji
H
Kobayashi
Takehiko
T
D000251:Adenosine Triphosphatases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002842:Chromatids / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000235:genetics / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005784:Gene Amplification; D018628:Gene Dosage; D005800:Genes, Fungal; D020459:Genes, rRNA; D016681:Genome, Fungal; D042822:Genomic Instability; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D046912:Multiprotein Complexes / Q000378:metabolism; D009153:Mutagens / Q000494:pharmacology; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D014158:Transcription, Genetic; D015854:Up-Regulation; D000097722:Cohesins
D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D008741:Methyl Methanesulfonate; D046912:Multiprotein Complexes; D009153:Mutagens; D012331:RNA, Fungal; D000097722:Cohesins; C108312:condensin complexes