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

Translin是一种DNA结合蛋白，能特异性识别人类淋巴肿瘤中涉及1p32、3q27、5q31、8q24、9q34、9q34.3、10q24、11p13、11q13、14q11、14q32、14q32.1、17q22、18q21、19p13和22q11的许多染色体易位中的共同序列基序ATGCAG和GCCC[A/T][G/C][G/C][A/T]。DNA结合蛋白在很大程度上是识别其目标序列的二聚体或四聚体。在这里，我们证明了Translin，一种新的单链DNA末端结合蛋白，形成了一个环状结构，在整个进化过程中都是保守的，这种结构是其DNA结合活性的原因。人类Translin亮氨酸拉链基序1eu184和leu191处的点突变导致多聚体结构丢失和DNA结合丧失。然而，碱基区R86、H88、H90到T86、N88、N90的点突变完全抑制了DNA结合活性，而不影响多聚体结构。这些结果支持了Translin的DNA结合域是与其碱性区域(氨基酸86-97)多肽结合形成环状结构的观点。

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.