Molecular mechanisms of chromosomal rearrangement caused by topological changing of DNA.

• Project/Area Number: 25291077
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Genetics/Chromosome dynamics
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Maki Hisaji 奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (20199649)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 染色体再編・維持 / 遺伝的不安定性 / 繰り返し配列

Outline of Final Research Achievements

Various kinds of repetitive sequence present in genomes of many species are known to be a cause of genetic instability which leads to genetic diseases and cancer. We found that a long inverted repeat is transformed to a cruciform DNA in a manner dependent on DNA replication. E. coli SbcCD appeared to have a novel enzymatic acitivity that cleaves such a cruciform DNA, and this enzyme perhaps causes the genetic instability at long inverted repeats.

Research Products

• [Int'l Joint Research] University of Edinburgh(英国)
• [Journal Article] Long inverted repeat transiently stalls DNA replication by forming hairpin structures on both leading and lagging strands (2016)
  • Author(s): Lai P.J., Lim C.T., Le H.P., Katayama T., Leach D.R.F, Furukohri A＊., Maki H.
  • Journal Title: Genes to Cells Volume: 21 Issue: 2 Pages: 136-145
  • DOI: 10.1111/gtc.12326
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A novel mode of nuclease action is revealed by the bacterial Mre11/Rad50 complex (2015)
  • Author(s): Lim C.T., Lai P.J., Leach D.R.F, Maki H., Furukohri A
  • Journal Title: Nucleic Acids Research Volume: 43 Pages: 9804-9816
  • DOI: 10.1093/nar/gkv855
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Short CCG repeat in huntingtin gene is an obstacle for replicative DNA polymerases, potentially hampering progression of replication fork. (2015)
  • Author(s): Le HP, Masuda Y, Tsurimoto T, Maki S, Katayama T, Furukohri A, Maki H.
  • Journal Title: Genes Cells. Volume: 10 Issue: 10 Pages: 817-833
  • DOI: 10.1111/gtc.12275
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Recombinase and translesion DNA polymerase decrease the speed of replication fork progression during the DNA damage response in Escherichia coli cells. (2015)
  • Author(s): Tan K.W., Pham M.T., Furukohri A, Maki H. and Akiyama T.M.
  • Journal Title: Nucleic Acids Research Volume: 43 Issue: 3 Pages: 1715-1725
  • DOI: 10.1093/nar/gkv044
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] DNA polymeraes IV mediates efficient and quick recovery at N2-dG adducts. (2014)
  • Author(s): Ikeda M, Furukohri A, Philippin G, Loechler E, Akiyama MT, Katayama T, Fuchs RP, Maki H.
  • Journal Title: Nucleic Acids Research Volume: 42 Issue: 13 Pages: 8461-8472
  • DOI: 10.1093/nar/gku547
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A single-molecule approach to DNA replication in Escherichia coli cells demonstrated that DNA polymerase III is a major determinant of fork speed. (2013)
  • Author(s): Pham M.T., Tan K.W., Sakumura Y., Okumura K., Maki H. and Akiyama T.M.
  • Journal Title: Molecular Microbiology Volume: 90 Issue: 3 Pages: 584-596
  • DOI: 10.1111/mmi.12386
  • Peer Reviewed
• [Presentation] 大腸菌のrecAまたはdinB遺伝子の過剰発現による複製フォーク進行の遅延 (2015)
  • Author(s): Tan Kang Wei, Pham Minh Tuan, 古郡麻子, 真木壽治, 秋山昌広
  • Organizer: 日本分子生物学会第３８回年会
  • Place of Presentation: 神戸ポートアイランド、兵庫県神戸市
  • Year and Date: 2015-12-01
• [Presentation] 大腸菌の栄養環境が酸化ＤＮＡ損傷と活性酸素種に与える影響 (2015)
  • Author(s): 布瀬翔平, Tom Conrad, 安藤さやか, 豊本奈美江, 中村葵, 秋山昌広, 真木壽治
  • Organizer: 日本遺伝学会第８７回大会
  • Place of Presentation: 東北大学、宮城県仙台市
  • Year and Date: 2015-09-26
• [Presentation] 低ｐＨ培養環境は大腸菌細胞内の酸化ＤＮＡ損傷レベルを上昇させる (2015)
  • Author(s): 宮原亮太, 真木壽治
  • Organizer: 日本遺伝学会第８７回大会
  • Place of Presentation: 東北大学、宮城県仙台市
  • Year and Date: 2015-09-26
• [Presentation] Biochemical analysis reveals a novel action of bacterial Mre11/Rad50 complex (2015)
  • Author(s): 古郡麻子, Lim Chew Theng, Lai Pey Jiun, David R.F. Leach, 真木壽治
  • Organizer: 日本遺伝学会第８７回大会
  • Place of Presentation: 東北大学、宮城県仙台市
  • Year and Date: 2015-09-25
  • Invited
• [Presentation] recAまたはdinB遺伝子の過剰発現による複製フォーク速度の低下 (2015)
  • Author(s): Tan Kang Wei, Pham Minh Tuan, 古郡麻子, 真木壽治, 秋山昌広
  • Organizer: 日本遺伝学会第８７回大会
  • Place of Presentation: 東北大学、宮城県仙台市
  • Year and Date: 2015-09-25
• [Presentation] 大腸菌DNAポリメラーゼＩの細胞内機能におけるβクランプの役割 (2015)
  • Author(s): 山本崇史, 真木壽治
  • Organizer: 日本遺伝学会第８７回大会
  • Place of Presentation: 東北大学、宮城県仙台市
  • Year and Date: 2015-09-25
• [Presentation] ヌクレオチドプールとＤＮＡの酸化損傷に起因する突然変異 (2015)
  • Author(s): 真木壽治
  • Organizer: 日本遺伝学会第８７回大会
  • Place of Presentation: 東北大学、宮城県仙台市
  • Year and Date: 2015-09-24
  • Invited
• [Presentation] 大腸菌のSOS応答による複製フォークの進行速度の低下 (2014)
  • Author(s): Tang Kang Wei、Pham Minh Tuan、古郡麻子、奥村克純、真木寿治、秋山昌広
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜・神奈川県・横浜市
  • Year and Date: 2014-11-25 – 2014-11-27
  • Invited
• [Presentation] Escherichia coli DNA polymerase IV mediates quick recpovery of repliaction forks stalled at N2-dG adducts. (2014)
  • Author(s): Furukohri, A., Ikead, M., Akiyama, M., Katayama, T., Fuchs R.P., and Maki, H.
  • Organizer: The 9th 3R International Symposium
  • Place of Presentation: 御殿場高原ホテル・静岡県・御殿場市
  • Year and Date: 2014-11-11 – 2014-11-21
• [Presentation] A single molecule approach to DNA replication in Escherichia coli cells demonstrated that DNA polymerae III is a major determinant of fork speed. (2014)
  • Author(s): Pham, TM., Tan, K.W., Sakumura, Y., Okumura,K., Furukohri, A., Maki, H.,and Akiyama, T.M.
  • Organizer: The 9th 3R International Symposium
  • Place of Presentation: 御殿場高原ホテル・静岡県・御殿場市
  • Year and Date: 2014-11-11 – 2014-11-21
• [Presentation] 大腸菌損傷乗り越え型 DNA Polymerase IV の複製フォークにおける役割 (2014)
  • Author(s): 古郡麻子、池田美央、西川義人、秋山昌広、片山 勉、Robert P. Fuchs、真木寿治
  • Organizer: 日本遺伝学会 第86回大会
  • Place of Presentation: 長浜バイオ大学・滋賀県・長浜市
  • Year and Date: 2014-09-17 – 2014-09-19
• [Presentation] 大腸菌のSOS応答による複製フォーク速度の減速 (2014)
  • Author(s): Tang Kang Wei、Pham Minh Tuan、古郡麻子、奥村克純、真木寿治、秋山昌広
  • Organizer: 日本遺伝学会 第86回大会
  • Place of Presentation: 長浜バイオ大学・滋賀県・長浜市
  • Year and Date: 2014-09-17 – 2014-09-19
• [Presentation] A short CCG run in the Huntingtin gene is an obstacle for replicative DNA polymerases, potentially hampering fork progression. (2014)
  • Author(s): Hang, L.P., Furukohri, A., Masuda, Y., Maki, S., Katayama, T., Fuchs R.P., and Maki, H.
  • Organizer: DNA polymerases: Biology, Diseases and Biomediacal Appliatiuon Conference 2014
  • Place of Presentation: Robinson college, Cambridge (England)
  • Year and Date: 2014-08-31 – 2014-09-04
• [Presentation] Escherichia coli DNA polymerase IV mediates quick recpovery of repliaction forks stalled at N2-dG adducts. (2014)
  • Author(s): Furukohri, A., Ikead, M., Akiyama, M., Katayama, T., Fuchs R.P., and Maki, H.
  • Organizer: DNA polymerases: Biology, Diseases and Biomediacal Appliatiuon Conference 2014
  • Place of Presentation: Robinson college, Cambridge (England)
  • Year and Date: 2014-08-31 – 2014-09-04
• [Presentation] A single molecule approach to DNA replication in Escherichia coli cells demonstrated that DNA polymerae III is a major determinant of fork speed. (2014)
  • Author(s): Pham, TM., Tan, K.W., Sakumura, Y., Okumura,K., Furukohri, A., Maki, H.,and Akiyama, T.M.
  • Organizer: DNA polymerases: Biology, Diseases and Biomediacal Appliatiuon Conference 2014
  • Place of Presentation: Robinson college, Cambridge (England)
  • Year and Date: 2014-08-31 – 2014-09-04
• [Presentation] 大腸菌細胞におけるDNA複製フォークの進行速度に関する一分子解析. (2013)
  • Author(s): Pham Minh Tuan、Tang Kang Wei、作村諭一、奥村克純、真木寿治、秋山昌広
  • Organizer: 第36回 日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド、神戸市
• [Presentation] 大腸菌細胞における複製フォークの進行速度に関する一分子解析. (2013)
  • Author(s): Pham Minh Tuan、Tang Kang Wei、作村諭一、奥村克純、真木寿治、秋山昌広
  • Organizer: 第22回 DNA複製･組換え･修復ワークショップ
  • Place of Presentation: ホテルニュー水戸屋、仙台市
• [Presentation] 大腸菌 Pol IV の働きにより複製フォークはN2-dG DNA損傷を効率よく乗り越えて進行を続ける (2013)
  • Author(s): 古郡麻子、池田美央、秋山昌広、片山 勉、Robert P. Fuchs、真木寿治
  • Organizer: 第22回 DNA複製･組換え･修復ワークショップ
  • Place of Presentation: ホテルニュー水戸屋、仙台市
• [Presentation] 自然突然変異とDNAポリメラーゼの分子機構研究 (2013)
  • Author(s): 真木寿治
  • Organizer: 日本遺伝学会 第85回大会
  • Place of Presentation: 慶応大学日吉キャンパス、横浜市
  • Invited
• [Presentation] A sequence flanking CAG/CTG trinucleotide repeats in the gene responsible for Hiungtington's disease has a potential for blocking DNA polymerases and may cause the replication fork arrest. (2013)
  • Author(s): Phuong Hang Le、古郡麻子、増田雄司、片山 勉、真木智子、真木寿治
  • Organizer: 日本遺伝学会 第85回大会
  • Place of Presentation: 慶応大学日吉キャンパス、横浜市
• [Presentation] DNA polymerase III is a major determinat of replication fork speed in Escherichia coli. (2013)
  • Author(s): Pham Minh Tuan、Tang Kang Wei、作村諭一、奥村克純、真木寿治、秋山昌広
  • Organizer: 日本遺伝学会 第85回大会
  • Place of Presentation: 慶応大学日吉キャンパス、横浜市
• [Presentation] 大腸菌細胞のDNA複製フォーク速度の単分子解析. (2013)
  • Author(s): Pham Minh Tuan、Tang Kang Wei、作村諭一、奥村克純、真木寿治、秋山昌広
  • Organizer: 日本遺伝学会 第85回大会
  • Place of Presentation: 慶応大学日吉キャンパス、横浜市
• [Presentation] 大腸菌細胞のDNA複製フォーク速度の単分子解析. (2013)
  • Author(s): Pham Minh Tuan、Tang Kang Wei、作村諭一、奥村克純、真木寿治、秋山昌広
  • Organizer: 第10回 21世紀大腸菌研究会
  • Place of Presentation: ラフォーレ修善寺、伊豆市