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Nature:發現哺乳動物染色體聯會必需的酶

來源:Nature
發現哺乳動物染色體聯會必需的酶
    在減數分裂和同源DNA修復中,會形成一個被稱為“霍利迪連結體”(Hollidayjunction)的四鏈DNA中間體。這個結構以共價鍵方式連接兩個DNA分子,因此必須將其拆解,才能讓染色體正確分離和復制。
   1991年,研究人員發現,大腸桿菌中的ruvC基因的產物為**“霍利迪連結體”解離酶。不過,哺乳動物相應的酶卻并不好尋找,但經過17年之后,它們終于被發現了。人體中的這種酶是一種被稱為GEN1的蛋白,酵母中的這種酶是其直系同源蛋白,即Yen1。二者都是結構特異性核酶的Rad2/XPG家族的成員。(創賽新聞中心 canspecsci.com)

創賽推薦原始出處:

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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