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Nature:发现哺乳动物染色体联会必需的酶

来源:Nature
发现哺乳动物染色体联会必需的酶
    在减数分裂和同源DNA修复中,会形成一个被称为“霍利迪连结体”(Hollidayjunction)的四链DNA中间体。这个结构以共价键方式连接两个DNA分子,因此必须将其拆解,才能让染色体正确分离和复制。
   1991年,研究人员发现,大肠杆菌中的ruvC基因的产物为**“霍利迪连结体”解离酶。不过,哺乳动物相应的酶却并不好寻找,但经过17年之后,它们终于被发现了。人体中的这种酶是一种被称为GEN1的蛋白,酵母中的这种酶是其直系同源蛋白,即Yen1。二者都是结构特异性核酶的Rad2/XPG家族的成员。(创赛新闻中心 canspecsci.com)

创赛推荐原始出处:

Nature 456, 357-361 (20 November 2008) |doi:10.1038/nature07470
Identification of Holliday junction resolvases from humans andyeast
Stephen C. Y. Ip1,3, Ulrich Rass1,3, Miguel G. Blanco1,3, Helen R.Flynn2, J. Mark Skehel2 & Stephen C. West1
1 Genetic Recombination Laboratory,
2 Protein Analysis and Proteomics Laboratory, Cancer Research UK,London Research Institute, Clare Hall Laboratories, South Mimms,Herts EN6 3LD, UK
3 These authors contributed equally to this work.
Abstract
Four-way DNA intermediates, also known as Holliday junctions, areformed during homologous recombination and DNA repair, and theirresolution is necessary for proper chromosome segregation. Here weidentify nucleases from Saccharomyces cerevisiae and human cellsthat promote Holliday junction resolution, in a manner analogous tothat shown by the Escherichia coli Holliday junction resolvaseRuvC. The human Holliday junction resolvase, GEN1, and its yeastorthologue, Yen1, were independently identified using two distinctexperimental approaches: GEN1 was identified by mass spectrometryfollowing extensive fractionation of HeLa cell-free extracts,whereas Yen1 was detected by screening a yeast gene fusion libraryfor nucleases capable of Holliday junction resolution. Theeukaryotic Holliday junction resolvases represent a new subclass ofthe Rad2/XPG family of nucleases. Recombinant GEN1 and Yen1 resolveHolliday junctions by the introduction of symmetrically relatedcuts across the junction point, to produce nicked duplex productsin which the nicks can be readily ligated.

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