最近,英国爱丁堡大学的科学家发现了一种酶,该酶能在基因组的任何位置中“剪切”和“粘贴”(cut-and-paste)“垃圾”DNA。这项发现发表于近期的Cell杂志上,或将加速基因疗法的发展。
在基因转座(DNA transposition)过程中,发生转移的基因对邻近的基因的功能会产生重大的影响。在人类基因组中,抗体基因的重排使得免疫系统更有效地对抗感染。转移基因的可“剪切”和“粘贴”的性质如今已应用于多种科学研究和医疗应用上。
占人类基因组中近一半的“垃圾”DNA,之前一直被认为是没有意义的。而在该研究中,研究人员发现,在这种“剪切”和“粘贴”的机制中,“垃圾”DNA的移动对细胞会产生影响。
研究人员Julia Richardson说,通过了解这种酶如何引起基因转座,可以更好调整和控制该酶。(生物谷Bioon.com)
生物谷国庆专题:新中国生命科学60年
生物谷推荐原始出处:
Cell Volume 138, Issue 6, doi:10.1016/j.cell.2009.07.012
Molecular Architecture of the Mos1 Paired-End Complex: The Structural Basis of DNA Transposition in a Eukaryote
Julia M. Richardson1,Sean D. Colloms2, David J. Finnegan1 and Malcolm D. Walkinshaw1
1School of Biological Sciences, University of Edinburgh, The King's Buildings, Mayfield Road, Edinburgh, EH9 3JR, Scotland
2Xermit, 44 Colchester Drive, Glasgow, G12 0NF, Scotland
A key step in cut-and-paste DNA transposition is the pairing of transposon ends before the element is excised and inserted at a new site in its host genome. Crystallographic analyses of the paired-end complex (PEC) formed from precleaved transposon ends and the transposase of the eukaryotic element Mos1 reveals two parallel ends bound to a dimeric enzyme. The complex has a trans arrangement, with each transposon end recognized by the DNA binding region of one transposase monomer and by the active site of the other monomer. Two additional DNA duplexes in the crystal indicate likely binding sites for flanking DNA. Biochemical data provide support for a model of the target capture complex and identify Arg186 to be critical for target binding. Mixing experiments indicate that a transposase dimer initiates first-strand cleavage and suggest a pathway for PEC formation.