ゲノムの安定な維持における組換えの役割
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概要
- 論文の詳細を見る
The focus of our studies is on understanding the roles of recombination in mitotic cells, that is, how recombination contributes to genome maintenance and how it is regulated so as to suppress genome instability. To that end, it is important to obtain an overview of genome in-stability, and we have hence developed an assay system that analyzes the genetic events responsible for loss of a heterozygous marker (LOH) in yeast diploid cells. This assay allows the quantitative identification of various genetic alterations including chromosome loss, different types of chromosome rearrangements, and point mutations, all of which occurred within the same population subjected to the analysis. In addition, to examine the breakpoints of chromosomal rearrangement at the nucleotide level, we have established a PCR-based method to quantify the ploidy at a series of loci throughout the chromosome. By exploiting the molecular genetic systems, we showed that recombination plays both positive and negative roles in the maintenance of genome stability. In other words, spontaneous DNA lesions capable of triggering recombination occur at a strikingly high frequency throughout the genome during normal cell growth; the majority of lesions are processed precisely through sister chromatid recombination, and a part of that process leads to genetic alterations. We also found that recombination is regulated at multiple steps in such a way as to suppress genome instability, presumably to control its dual roles. In this review, I also summarize the backgrounds of our studies as well as the findings of recent cacner studies that reveal the roles of recombination regulatory elements as tumour suppressors.
- 福岡歯科大学学会の論文
- 2008-06-30