Sperm-specific mechanism that induces the gross chromosomal rearrangements

诱导染色体重排的精子特异性机制

• 批准号: 21390101
• 负责人: KURAHASHI Hiroki
• 金额: $ 11.81万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390101/
• 关键词: 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

Gross chromosomal rearrangements(GCRs) are often generated by illegitimate repair between two DNA breakages at regions with nucleotide sequences that potentially adopt a non-B DNA structure. We previously established a plasmid-based model system that recapitulates palindrome-mediated recurrent translocations in humans, and demonstrated that cruciform DNA is required for the rearrangements. In this study, we show that two sequential reactions that cleave the cruciform structures induce the translocation : GEN1-mediated resolution that cleaves diagonally at the four-way junction of the cruciform, and Artemis-mediated opening of the subsequently formed hairpin ends. These two intrinsic pathways that normally fulfill vital functions independently, Holliday junction resolution in homologous recombination and coding joint formation in rearrangement of antigen-receptor genes, act upon the unusual DNA conformation in concert and lead to these recurrent GCRs in humans.

总染色体重排（GCR）通常是由两个DNA断裂之间的非法修复产生的，这些DNA断裂位于具有潜在采用非B DNA结构的核苷酸序列的区域。我们以前建立了一个基于质粒的模型系统，概括回文介导的复发性易位在人类中，并证明，十字形DNA是所需的重排。在这项研究中，我们表明，两个连续的反应，切割十字形结构诱导易位：GEN1介导的决议，对角切割十字形的四路交界处，和Artemis介导的开放随后形成的发夹末端。这两个内在的途径，通常独立地履行重要的功能，霍利迪连接决议同源重组和编码接头形成抗原受体基因的重排，共同作用于不寻常的DNA构象，并导致这些复发性GCR在人类。

项目成果

Global gene expression profiling in kidneys of PPAR-gamma agonist-treated PCK rats, an orthologous model of human ARPKD

PPAR-γ 激动剂治疗的 PCK 大鼠（人类 ARPKD 的直系同源模型）肾脏中的整体基因表达谱

• 发表时间: 2011
• 作者: Yoshihara D;Kugita M;Kurahashi H;Morita M;Hiki Y;Yamaguchi T;Aukema HM;Wallace DP;Calvet JP;Toyohara T;Abe T;Nagao S
• 通讯作者: Nagao S

Identification of a novel palindrome mediated translocation associated with the t(3 ; 8) of hereditary renal cancer

鉴定与遗传性肾癌 t(3;8) 相关的新型回文介导的易位

• 发表时间: 2011
• 作者: Kato T;Sheridan MB;Hacker AM;Inagaki H;Glover TW;Plon SE;Drabkin HA;Gemmill RM;Kurahashi H;Emanuel BS
• 通讯作者: Emanuel BS

Serum Neutrophil Gelatinase Associated Lipocalin During the Early Postoperative Period Predicts the Recovery of Graft Function After Kidney Transplantation From Donors After Cardiac Death

• DOI: 10.1016/j.juro.2012.01.033
• 发表时间: 2012-06-01
• 期刊: JOURNAL OF UROLOGY
• 影响因子: 6.6
• 作者: Kusaka, Mamoru;Iwamatsu, Fumi;Hoshinaga, Kiyotaka
• 通讯作者: Hoshinaga, Kiyotaka

Mutations of the SYCP3 Gene in Women with Recurrent Pregnancy Loss

• DOI: 10.1016/j.ajhg.2008.12.002
• 发表时间: 2009-01-09
• 期刊: AMERICAN JOURNAL OF HUMAN GENETICS
• 影响因子: 9.8
• 作者: Bolor, Hasbaira;Mori, Terumi;Kurahashi, Hiroki
• 通讯作者: Kurahashi, Hiroki

Global expression profiles in 1-hour biopsy specimens of human kidney transplantation from donors after cardiac death

心脏死亡后捐献者肾移植 1 小时活检标本中的整体表达谱

• 发表时间: 2009
• 期刊: Cell Transplantation 18
• 作者: Kusaka M;Kuroyanagi Y;Mori T;Nagaoka K;Sasaki H;Maruyama T;Hayakawa K;Shiroki R;Kurahashi H;Hoshinaga K
• 通讯作者: Hoshinaga K