DNA secondary structure drives chromosomal dynamics

• Project/Area Number: 19390097
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Fujita Health University
• Principal Investigator: KURAHAS Hihiroki Fujita Health University, 総合医科学研究所, 教授 (30243215)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 染色体転座 / 切断点 / 回文配列 / パリンドローム / 十字架型DNA / 非B型DNA / 染色体再構成 / 染色体構造異常 / 十字架型

Research Abstract

t(11 ; 22)転座は、現在知られている唯一の反復性の生殖細胞系列染色体転座である。転座保因者は無症状だが、無精子症、反復性流産、子の染色体不均衡による先天異常など、再生産に問題が生じる。本研究では、2つの転座切断点をそれぞれベクターに組み込み、細胞株に導入すると転座反応が起きる、という転座のモデル系を確立した。この転座反応は切断点の配列が特殊な立体構造をとったときのみ発生し、このDNAの立体構造の異常によりDNAが不安定になることが、繰り返し起こる染色体転座の原因であることを証明した。

Research Products

• [Journal Article] Two different forms of palindrome resolution in the human genome : deletion or translocation (2008)
  • Author(s): Kato, T., Inagaki, H., Kogo, H., Ohye, T., Yamada, K., Emanuel, B. S., Kurahashi, H.
  • Journal Title: Hum. Mol. Genet 17 Pages: 1184-1191
  • Peer Reviewed
• [Journal Article] Increased levels of pregnancy-associated plasma protein-A2 in the serum of pre-eclamptic patients (2008)
  • Author(s): Nishizawa, H., Pryor-Koishi, K., Suzuki, M., Kato, T., Kogo, H., Sekiya, T., Kurahashi, H., Udagawa, Y.
  • Journal Title: Mol. Hum. Reprod 14 Pages: 595-602
  • Peer Reviewed
• [Journal Article] Two different forms of palindrome resolution in the human genome : deletion or translocation. (2008)
  • Author(s): Kato T, Inagaki H, Kogo H, Ohye T, Yamada K, Emanuel BS, Kurahashi H
  • Journal Title: Human Molecular Genetics 17 Pages: 1184-91
  • Peer Reviewed
• [Journal Article] Increased levels of pregnancy-associated plasma protein-A2 in the serum of pre-eclamptic patients. (2008)
  • Author(s): Nishizawa H, Pryor-Koishi K, S uzuki M, Kato T, Kogo H, Sekiya T, Kurahashi H, Udagawa Y
  • Journal Title: Molecular Human Reproduction 14 Pages: 595-602
  • Peer Reviewed
• [Journal Article] Mouse model for allogeneic fetal rejection recapitulates humanpre-eclampsia. (2008)
  • Author(s): Nishizawa H, Hasegawa K, Suzuki M, Achiwa Y, Kato T, Saito K, Kurahashi H, Udagawa Y
  • Journal Title: Journal of Obstetrics Gynaecology Research 34 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Calcium channel inhibition with verapamil accelerates polycystic kidney disease progression in the Cy/+rat. (2008)
  • Author(s): Nagao s, Nishii K, Yoshihara D, Kurahashi H, et al.
  • Journal Title: Kidney Int 73 Pages: 269-77
  • Peer Reviewed
• [Journal Article] Global gene expression profiling on renal scarring in rat model of pyelonephritis. (2008)
  • Author(s): Ichino M, Mori T, Kusaka M, Kuroyanagi Y, Ishikawa K, Shiroki R, Kurahashi H, et al.
  • Journal Title: Pediatric Nephrology 23 Pages: 1059-71
  • Peer Reviewed
• [Journal Article] Up-regulated cytokine inducible SH2-containing protein expression in allergen-stimulated T cells from hen's egg-allergic patients. (2008)
  • Author(s): Nakajima Y, Tsuge I, Kondo Y, Komatsubara R, Hirata N, Kakami M, Kurahashi H., et al.
  • Journal Title: Clinical Experimental Allergy 38 Pages: 1499-506
  • Peer Reviewed
• [Journal Article] Serum neutrophil gelatinase-associated lipocalin as a predictor of organ recovery from delayed graft function after kidney tran splantation applying donation after cardiac death (2008)
  • Author(s): Kusaka M, Kuroyanagi Y, Mori T, Nagaoka K, Sasaki H, Maruyama T, Kurahashi H, et al.
  • Journal Title: Cell Transplantation 17 Pages: 129-34
  • Peer Reviewed
• [Journal Article] Molecular clonong of a translocation hotspot in 22q11 (2007)
  • Author(s): Kurahashi, H., Inagaki, H., Hosoba. E., Kato, T., Ohye, T., Kogo, H., Emanuel, B. S.
  • Journal Title: Genome Res 17 Pages: 461-469
  • Peer Reviewed
• [Journal Article] Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype (2007)
  • Author(s): Kano, H., Kurahashi, H., Toda, T.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 104 Pages: 19034-19039
  • Peer Reviewed
• [Journal Article] Age has no effect on de novo constitutional t(11 ; 22) translocation frequency in sperm (2007)
  • Author(s): Kato, T., Yamada, K., Inagaki, H., Kogo, H., Ohye, T., Emanuel, B.S., Kurahashi, H.
  • Journal Title: Fertil Steril 88 Pages: 1446-1448
  • Peer Reviewed
• [Journal Article] Cruciform extrusion propensity of human translocationmediating palindromic AT-rich repeats (2007)
  • Author(s): Kogo, H., Inagaki, H., Ohye, T., Kato, T., Emanuel, B.S., Kurahashi, H.
  • Journal Title: Nucleic Acids Res 35 Pages: 1198-1208
  • Peer Reviewed
• [Journal Article] CDH1 is a specific marker for undifferentiated spermatogonia in mouse testes (2007)
  • Author(s): Tokuda, M., Kadokawa, Y., Kurahashi, H., Marunouchi, T.
  • Journal Title: Biol. Reprod. 76 Pages: 130-141
  • Peer Reviewed
• [Journal Article] Molecular clonong of a translocation hotspot in 22q11. (2007)
  • Author(s): Kurahashi, H., Inagaki, H., Hosoba. E., et. al.
  • Journal Title: Genome Research 17 Pages: 461-469
  • Peer Reviewed
• [Journal Article] Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats. (2007)
  • Author(s): Kogo, H., Inagaki, H., Kurahashi, H., et. al.
  • Journal Title: Nucleic Acids Research 35 Pages: 1198-1208
  • Peer Reviewed
• [Journal Article] Age has no effect on de novo constitutional t(11;22)translocation frequency in sperm. (2007)
  • Author(s): Kato, T., Yamada, K., Kurahashi, H., et. al.
  • Journal Title: Fertility & Sterility 88 Pages: 1446-1448
  • Peer Reviewed
• [Journal Article] CDH1 is a specific marker for undifferentiated spermatogonia in mouse testes. (2007)
  • Author(s): Tokuda, M., Kadokawa, Y., Kurahashi, H., et. al.
  • Journal Title: Biology of Reproduction 76 Pages: 130-141
  • Peer Reviewed
• [Journal Article] Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype. (2007)
  • Author(s): Kano, H., Kurahashi, H., Toda, T.
  • Journal Title: Proceedings of National Academy of Science of the U.S.A., 104 Pages: 19034-19039
  • Peer Reviewed
• [Journal Article] Microarray analysis of differentially expressed fetal genes in placental tissue derived from early and late onset severe pre-eclampsia. (2007)
  • Author(s): Nishizawa, H., Pryor-Koishi, K., Kurahashi, H., et. al.
  • Journal Title: Placenta 28 Pages: 487-497
  • Peer Reviewed
• [Journal Article] The etiological role of allogeneic fetal rejection in pre-eclampsia. (2007)
  • Author(s): Nishizawa, H., Hasegawa, K. Kurahashi, H., et. al.
  • Journal Title: American Journal of Reproductive Immunology 58 Pages: 11-20
  • Peer Reviewed
• [Journal Article] Genome-wide expression profile in rat model of renal isografts from brain dead donors. (2007)
  • Author(s): Kusaka, M., Kuroyanagi, Y., Kurahashi, H., et. al.
  • Journal Title: Transplantation 83 Pages: 62-70
  • Peer Reviewed
• [Journal Article] Overproduction of the follistatin-related gene protein in the placenta and maternal serum of women with pre-eclampsia. (2007)
  • Author(s): Pryor-Koishi, K., Nishizawa, H., Kurahashi, H., et. al.
  • Journal Title: BJOG 114 Pages: 1128-1137
  • Peer Reviewed
• [Journal Article] Two different forms of palindrome resolution in the human genome: deletion or translocation.
  • Author(s): Kato, T., Inagaki, H., Kurahashi, H., et. al.
  • Journal Title: Human Molecular Genetics (印刷中)
  • Peer Reviewed
• [Journal Article] Mouse model for allogeneic fetal rejection recapitulates human pre-eclampsia.
  • Author(s): Nishizawa, H., Hasegawa, K., Kurahashi, H., et. al.
  • Journal Title: Journal of Obstetrics and Gynaecology Research (印刷中)
  • Peer Reviewed
• [Journal Article] Calcium channel inhibition with verapamil accelerates polycystic kidney disease progression in the Cy/+rat.
  • Author(s): Nagao, S., Nishii, K., Kurahashi, H., et. al.
  • Journal Title: Kidney International (印刷中)
  • Peer Reviewed
• [Journal Article] Serum neutrophil gelatinase-associated lipocalin as a predictor of organ recovery from delayed graft function after kidney transplantation applying donation after cardiac death.
  • Author(s): Kusaka, M., Kuroyanagi, Y., Kurahashi, H., et. al.
  • Journal Title: Cell Transplantation (印刷中)
  • Peer Reviewed
• [Journal Article] Global gene expression profiling on renal scarring in rat model of pyelonephritis.
  • Author(s): Ichino, M., Mori, T., Kurahashi, H., et. al.
  • Journal Title: Pediatric Nephrology (印刷中)
  • Peer Reviewed
• [Presentation] Artemis cleaves cruciform-forming palindromic DNA leading to recurrent translocation in humans. (2008)
  • Author(s): Inagaki H, Ohye T, Kogo H, Kato T, Tong M, Tsutsumi M, Emanuel BS, Kurahashi H
  • Organizer: ASHG AT/GI Satellite Meeting
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 2008-11-11
• [Presentation] Chromosomal instability mediated by non-B DNA : Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans. DNA Palindromes : Roles, consequences and implications of structurally ambivalent DNA (2008)
  • Author(s): Kurahashi, H.
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Saxtons River, USA
• [Presentation] Mutations of the SYCP3 gene in women with recurrent pregnancy loss (2008)
  • Author(s): Kurahashi, H.
  • Organizer: 58th annual meeting of American Society of Human Genetics
  • Place of Presentation: Philadelphia, USA
• [Presentation] Artemis cleaves cruciform-forming palindromic DNA leading to recurrent translocation in humans (2008)
  • Author(s): Inagaki, H., Ohye, T., Kogo, H., Kato, T., Tong, M., Tsutsumi, M., Emanuel., B. S., Kurahashi, H.
  • Organizer: 58th annual meeting of American Society of Human Genetics
  • Place of Presentation: Philadelphia, USA
• [Presentation] Possible post-meiotic origin of the constitutional t(11 ; 22) (2008)
  • Author(s): Kato, T., Inagaki, H., Kogo, H., Ohye, T., Yamada, K., Emanuel, B.S., Kurahashi, H.
  • Organizer: European Human Genetics Conference
  • Place of Presentation: Barcelona, Spain
• [Presentation] Chromosomal instability mediated by non-B DNA : Cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans. (2008)
  • Author(s): Kurahashi H.
  • Organizer: FASEB SRC. DNA Palindromes.
  • Place of Presentation: Saxtons River, VT
• [Presentation] Mutations of the SYCP3 gene in women with recurrent pregnancy loss. (2008)
  • Author(s): Kurahashi H. Bolor H, Mori T, Nishiyama S, Inagaki H, Kogo H, Tsutsumi M, Ohye T
  • Organizer: 58th annual meeting of ASHG
  • Place of Presentation: Philadelphia, PA
• [Presentation] Artemis cleaves cruciform-forming palindromic DNA leading to recurrent translocation in humans. (2008)
  • Author(s): Inagaki H, Ohye T, Kogo H, Kato T, Tong M, Tsutsumi M, Emanuel BS, Kurahashi H
  • Organizer: 58th annual meeting of ASHG
  • Place of Presentation: Philadelphia, PA
• [Presentation] Artemis cleaves cruciform-forming palindromic DNA leading to recurrent translocation in humans. (2008)
  • Author(s): Inagaki H, Ohye T, Kogo H, Kato T, Tong M, Tsutsumi M, Emanuel BS, Kurahashi H
  • Organizer: The 6th 3R Symposium
  • Place of Presentation: Kakegawa, Japan
• [Presentation] Possible post-meiotic origin of the constitutionalt(11 ; 22). (2008)
  • Author(s): Kato T, Inagaki H, Kogo H, Ohye T, Yamada K, Emanuel BS, Kurahashi H
  • Organizer: European Human Genetics Conference
  • Place of Presentation: Barcelona, Spain
• [Presentation] DNA secondary structure-forming propensity dictates translocation frequency (2007)
  • Author(s): Kato, T., Inagaki, H., Kogo, H., Ohye, T., Yamada, K., Emanuel, B. S., Kurahashi, H.
  • Organizer: European Human Genetics Conference 2007
  • Place of Presentation: Nice, France
• [Presentation] Possible post-meiotic origin of the constitutional t(11 ; 22) (2007)
  • Author(s): Kato, T., Inagaki, H., Kogo, H., Ohye, T., Tong, M., Emanuel, B. S., Kurahashi, H.
  • Organizer: 57th Annual Meeting of American Society of Human Genetics
  • Place of Presentation: San Diego, USA
• [Presentation] DNA secondary structure-forming propensity dictates translocation frequency. (2007)
  • Author(s): Kato, T., Inagaki, H., Kurahashi, H., et. al.
  • Organizer: European Human Genetics Conference 2007
  • Place of Presentation: Nice, France
• [Presentation] Possible post-meiotic origin of the constitutional t(11;22). (2007)
  • Author(s): Kato, T., Inagaki, H., Kurahashi, H., et. al.
  • Organizer: 57th Annual Meeting of American Society of Human Genetics
  • Place of Presentation: San Diego, USA
• [Remarks] 報道関連情報中日新聞掲載2008年12月25日
• [Remarks] 報道関連情報NHKテレビ2008年12月25日
• [Remarks] 報道関連情報NHKラジオ2008年12月25日
• [Remarks] 報道関連情報朝日新聞掲載2009年1月9日
• [Remarks]
  • URL: http://www.fujita-hu.ac.jp/~genome/mg/
• [Remarks]
  • URL: http://www.fujita-hu.ac.jp/~genome/mg/