セミナー情報

セミナー情報

Complex genome rearrangement in cancer cells caused by interplay between DNA replication and long non-coding RNA transcription

演題 Complex genome rearrangement in cancer cells caused by interplay between DNA replication and long non-coding RNA transcription
講演者 Dr. Takaaki Watanabe(Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cellular Biology, University of Cedars-Sinai Medical Center, CA, USA)
使用言語 English
日時 平成26年11月28日(金曜日) 14:00~15:00
場所 Large seminar room
内容
Recent advances in sequencing technologies have demonstrated the extent of the heterogeneity of cancer genomes and provided new insights into cancer genome evolution. The intra-tumor genetic heterogeneity could determine disease progression and clinical outcome in cancer medicine.
Here I show DNA replication stress can drive structural evolution of amplified extra-chromosomal segments (double minute chromosomes, DMs) in cancer cells. We first identified a natural stalling of DNA replication fork in DMs containing MYC oncogene, and demonstrated that lncRNA transcription impedes the fork progression. The key mediator was R-loop, transcription byproduct that constitutes a threat to genome integrity, becoming one of the hottest topics. We are now focusing on dysfunction of breast tumor suppressor BRCA2 in cancer cells as an important cause of R-loop accumulation.

I will also introduce catastrophic events forming complex genome rearrangement in cancer cells, as represented by chromothripsis, and discuss how our replication-based model could contribute to the complex rearrangements. Our results may highlight the new role of lncRNA transcription that could mark fork stalling-dependent fragile sites for genome instability.

問合せ先 原核生物分子遺伝学
真木 寿治 (maki@bs.naist.jp)

一覧へ戻る