Genome organization as a source of chromosomal instability in cancer.

2020 Fiscal Year Annual Research Report

• Project/Area Number: 19H03208
• Research Institution: Kyoto University
• Principal Investigator: Canela Andres 京都大学, 白眉センター, 特定准教授 (90837585)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: TOPOISOMERASEII / 染色体転座 / DNA 二重鎖切断 / 発かん / ゲノム安定性

Outline of Annual Research Achievements

During the fiscal year 2020:
1. Role of TOP2 in chromosomal organization
1.1. Analysis of genome organization in the absence of TOP2. I have generated cell lines that are deficient for TOP2β and TOP2α in combination with components of cohesin complex and I started to characterize the impact in genome organization and the role of TOP2 in chromatin loop formation using ChIP-seq and Hi-C.
1.2. Measure torsional stress across the genome produced by cohesin. I have set up different techniques to map in the genome torsional stress (entanglements and supercoiling) in the genome and I will apply them to study the torsional generated by cohesin advance.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

During the fiscal year 2020:
1. Role of TOP2 in chromosomal organization. I have made significative advances in this aim by accomplishing the points originally proposed and allows me to continue in the next fiscal year 2021.
2. The aim 2 it was already accomplished in 2019 and published.

Strategy for Future Research Activity

During the fiscal year 2021:
1. Role of TOP2 in chromosomal organization
1.1. Analysis of genome organization in the absence of TOP2. I will use the cell lines generated in the year 2020 to characterize the impact in genome organization and the role of TOP2 in chromatin loop formation.
1.2. I will map in the genome the torsional stress produced by cohesin.

Research Products

• [Journal Article] END-seq: An Unbiased, High-Resolution, and Genome-Wide Approach to Map DNA Double-Strand Breaks and Resection in Human Cells (2021)
  • Author(s): Wong N, John S, Nussenzweig A, Canela A.
  • Journal Title: Methods in Molecular Biology Volume: 2153 Pages: 9-31
  • DOI: 10.1007/978-1-0716-0644-5_2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes (2021)
  • Author(s): Huang SN, Michaels SA, Mitchell BB, Majdalani N, Vanden Broeck A, Canela A, Tse-Dinh YC, Lamour V, Pommier Y.
  • Journal Title: Science Advances Volume: 7 Pages: not yet
  • DOI: 10.1126/sciadv.abe0384
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Neuronal enhancers are hotspots for DNA single-strand break repair. (2021)
  • Author(s): Wu W, Hill SE, Nathan WJ, Paiano J, Callen E, Wang D, Shinoda K, van Wietmarschen N, Colon-Mercado JM, Zong D, De Pace R, Shih HY, Coon S, Parsadanian M, Pavani R, Hanzlikova H, Park S, Jung SK, McHugh PJ, Canela A, Chen C, Casellas R, Caldecott KW, Ward ME, Nussenzweig A.
  • Journal Title: Nature Volume: online Pages: not yet
  • DOI: 10.1038/s41586-021-03468-5
  • Peer Reviewed / Int'l Joint Research