ほ乳類細胞におけるDNA二本鎖切断修復と,p53によるゲノム安定化機構(第13回公開シンポジウム「環境変異原と遺伝子不安定性」)

概要

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Chromosomal double strand breaks (DSBs) occurring in mammalian cells can initiate genomic instability. They are usually repaired through either of two pathways end-joining (EJ) or homologous recombination (HR), and their misrepairs result in deletion, amplification, and translocation, which are common in human tumors. The tumor suppressor protein p53 is involved in maintaining genomic stability. We demonstrate here that the deficiency of wild-type p53 protein may allow unrepaired DSB to initiate chromosomal instability, and mutant-type p53 protein promotes illegitimate recombination leading to translocation. These results support a model in which p53 protein contributes to the maintenance of genomic integrity through recombinational repair. We also developed a system to trace the fate of DSBs occurring in a single copy gene of human genome using restriction endonuclease I-SceI. DSBs at the I-SceI site were repaired 100 times more frequently by EJ than HR. This system should be useful for understanding of mechanisms of DSB repair as well as serving as a model for DNA damage induced by low-dose irradiation.
日本環境変異原学会の論文
2002-11-13