Seminars

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

Title Complex genome rearrangement in cancer cells caused by interplay between DNA replication and long non-coding RNA transcription
Lecturer Dr. Takaaki Watanabe(Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cellular Biology, University of Cedars-Sinai Medical Center, CA, USA)
Language English
Date&Time 11/28/2014 (Fri) 14:00~15:00
Venue Large seminar room
Detail
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.

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

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