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）通常是通过具有可能采用非B DNA结构的核苷酸序列的两个DNA断裂之间的非法修复来产生的。我们以前建立了一个基于质粒的模型系统，该系统概括了人类中的腔介导的复发易位，并证明重排需要十字形DNA。在这项研究中，我们表明，两种裂解十字形结构的顺序反应诱导了易位：Gen1介导的分辨率，在十字形的四向交界处对角线切割，而Artemis介导的随后形成的发夹端的开口。这两种通常独立实现重要功能的内在途径，在抗原受体基因重排的同源重组和编码联合形成中的霍利迪连接分辨率作用于协同中不寻常的DNA构型，并导致人类中这些重新出现的GCR。

项目成果

Impaired DNA replication prompts deletions within palindromic sequences, but does not induce translocations in human cells

• DOI: 10.1093/hmg/ddp279
• 发表时间: 2009-09-15
• 期刊: HUMAN MOLECULAR GENETICS
• 影响因子: 3.5
• 作者: Kurahashi, Hiroki;Inagaki, Hidehito;Emanuel, Beverly S.
• 通讯作者: Emanuel, Beverly S.

CD9 gene variations are not associated with female infertility in humans.

CD9 基因变异与人类女性不孕症无关。

• 发表时间: 2010
• 期刊: Gynecol Obstet Invest
• 作者: Nishiyama S;Kishi T;Kato T;Suzuki M;Nishizawa H;Pryor-Koishi K;Sawada T;Nishiyama Y;Iwata N;Udagawa Y;Kurahashi H.
• 通讯作者: Kurahashi H.

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

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

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