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遺伝子発現統御第二研究部門(堀内研究室)が"Genes & Development"に論文掲載「酵母rRNA遺伝子における転写に依存した組み換えと複製フォーク衝突の役割」

DNAは誕生以来一人二役(転写と複製)を演じることを運命づけられてきたが、酵母のrRNA遺伝子リピート中に、両者が衝突する場所と条件を見出し、調べたところ組み換えが活性化されることが判明した。この組み換え活性はその遺伝子の発現量に比例することから、自然界でよく見られる「発現量の多い遺伝子のコピー数の増加」に働いている可能性を指摘した。(2003年6月3日 online版)

雑誌名: Genes & Development
発行年月日、ナンバー: June 15. 2004 17巻(12号)
論文タイトル: Transcription-dependent recombination and the role of fork collision in yeast rDNA
論文著者 : Yasushi Takeuchi‚ Takashi Horiuchi‚ and Takehiko Kobayashi
It is speculated that the function of the replication fork barrier (RFB) site is to avoid collision between the 35S rDNA transcription machinery and the DNA replication fork‚ because the RFB site is located near the 3'-end of the gene and inhibits progression of the replication fork moving in the opposite direction to the transcription machinery. However‚ the collision has never been observed in a blockless (fob1) mutant with 150 copies of rDNA. The gene FOB1 was shown previously to be required for replication fork blocking activity at the RFB site‚ and also for the rDNA copy number variation through unequal sister-chromatid recombination. This study documents the detection of fork collision in an fob1 derivative with reduced rDNA copy number (~20) using two-dimensional agarose gel electrophoresis. This suggests that most of these reduced copies are actively transcribed. The collision was dependent on the transcription by RNA polymerase I. In addition. the transcription stimulated rDNA copy number variation‚ and the production of the extrachromosomal rDNA circles (ERCs)‚ whose accumulation is thought to be a cause of aging. These results suggest that such a transcription-dependent fork collision induces recombination‚ and may function as a general recombination trigger for multiplication of highly transcribed single-copy genes.