Clarification of the mechanism involved in chromosomal translocations founded in hematologic neoplasms.

澄清血液肿瘤中发现的染色体易位涉及的机制。

• 批准号: 09671096
• 负责人: AOKI Katsunori
• 金额: $ 2.05万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671096/
• 关键词: hematologic neoplasm; chromosomal translocation; DNA binding protein; translin; functional domain; multimer formation; 遺伝子組み換え

Translin has been identified as a DNA binding protein that specifically recognizes the consensus sequences motifs, ATGCAG and GCCC[A/T][G/C][G/C][A/T], at breakpoint junctions in many chromosomal translocations in human lymphoid neoplasms involving 1p32, 3q27, 5q31, 8q24, 9q34, 9q34.3, 10q24, 11p13, 11q13, 14q11, 14q32, 14q32.1, 17q22, 18q21, 19p13, and 22q11. DNA binding proteins, for the most part, function as dimers or tetramers which recognize their target sequences. Here we show that Translin, a novel single-stranded DNA end binding protein, forms a ring-shaped structure conserved throughout evolution and that this structure is responsible for its DNA binding activity. Point mutations at 1eu184 and leu191 in the leucine zipper motif of human Translin resulted in loss of the multimeric structure and abrogation of DNA binding. Point mutations at R86, H88, H90 to T86, N88, N90 in one of the basic regions, however, completely inhibited the DNA binding activity without affecting the multimeric structure. These results support the view that the DNA binding domain of Translin is formed in the ring-shaped structure in combination with its basic region (amino acids 86-97) polypeptides.

转译蛋白是一种DNA结合蛋白，它特异性识别人类淋巴肿瘤中许多染色体易位的断裂点连接处的共有序列基序ATGCAG和GCCC[A/T][G/C][G/C][A/T]，这些易位涉及1 p32、3q 27、5 q31、8 q24、9 q34、9q34.3、10 q24、11 p13、11 q13、14 q11、14 q32、11 q27、11 q27、11 q28、11 q29、11 q29、1 14q32.1、17 q22、18 q21、19 p13和22 q11。DNA结合蛋白，在大多数情况下，作为识别其靶序列的二聚体或四聚体起作用。在这里，我们表明，翻译，一种新的单链DNA末端结合蛋白，形成一个环形结构，在整个进化过程中保守，这种结构是负责其DNA结合活性。人翻译蛋白亮氨酸拉链基序中1 eu 184和leu 191的点突变导致多聚体结构的丢失和DNA结合的废除。然而，在其中一个碱性区域中的R86、H88、H90至T86、N88、N90的点突变完全抑制DNA结合活性而不影响多聚体结构。这些结果支持这样的观点，即翻译蛋白的DNA结合结构域是与其碱性区（氨基酸86-97）多肽结合形成的环状结构。

项目成果

青木 克己: "Isolation and characterization of a cDNA encoding a Translin-like protein,TRAX" FEBS Letters. 401. 109-112 (1997)

Katsumi Aoki：“编码 Translin 样蛋白的 cDNA 的分离和表征，TRAX”FEBS Letters 401. 109-112 (1997)。

青木克己: "The DNA binding activity of Translin is mediated by a basic region in the ring-shaped structure conserved in evolution" FEBS Letter. (印刷中). (1999)

Katsumi Aoki：“Translin 的 DNA 结合活性是由进化中保守的环形结构中的基本区域介导的”FEBS Letter（1999 年）。

青木 克己: "Genomic Structure and Chromosomal Localization of the Gene Encaling Translin,a Recombination Hotspot Binding Drotein" GENOMICS. 43. 237-241 (1997)

Katsumi Aoki：“重组热点结合蛋白 Translin 基因的基因组结构和染色体定位”GENOMICS 43. 237-241 (1997)

Katsunori Aoki: "The DNA binding activity of Translin is mediatid by a basic region in the ring-shaped Structure conserved in evolution." FEBS Letter. (in press). (1999)

Katsunori Aoki：“Translin 的 DNA 结合活性是由进化中保守的环形结构中的基本区域介导的。”