第２３回　生命医科学セミナー（Biomedical Science Seminar）

演題：Can DNA double-strand breaks generated by Mus81 endonuclease contribute to replication restart and to genome stability?

演者：花田克浩博士

所属：Cancer Research UK laboratories, Weatherall Institute of Molecular Medicine,

　　　　The University of Oxford

日時：平成１９年１１月２９日（木）　１８：００～１９：００

場所：病院地区総合研究棟、１階１０５セミナー室

［セミナー内容の紹介］

A major challenge for all proliferating cells is to maintain genome integrity during DNA replication such that genetic information can be faithfully transmitted to daughter cells. Damage in the template DNA, induced by exogenous or endogenous agents, interferes with DNA replication, thereby increasing the risk of genome instability. Among the most severe types of DNA damage are DNA double-strand breaks (DSBs), which can trigger chromosome aberrations such as deletions, insertions and translocations. Therefore, preventing DSBs from forming should contribute to the maintenance of genome integrity. Paradoxically, faithful duplication of the genome requires structure-specific endonucleases such as the double-strand DNA break (DSB) generating enzyme RuvABC in Escherchia coli. These enzymes help to resolve problems at replication forks that have been disrupted due to DNA damage in the template. Much less is known about the identity of these enzymes in mammalian cells. Mus81 is the catalytic component of a eukaryotic structure-specific endonuclease that preferentially cleaves branched DNA substrates reminiscent of replication and recombination intermediates. Here, we addressed mechanisms by which Mus81 maintains chromosome stability. We found that Mus81 is involved in DSB formation in response to replication inhibition. Moreover, in the absence of chromosome processing by Mus81, recovery of stalled DNA replication forks is attenuated and chromosomal aberrations arise. We suggest that Mus81 suppresses chromosomal instability by converting potential detrimental replication-associated DNA structures into intermediates that are more amenable for DNA repair.

（共催：福岡医学会）