日本理化研究所日前發(fā)表新聞公報說,，該所研究人員發(fā)現(xiàn)酵母線粒體中的DNA（脫氧核糖核酸）在一定條件下進行同源重組時,，不像以前認為的那樣需要DNA形成超螺旋,。這一發(fā)現(xiàn)將為抗衰老等方面的生物醫(yī)學(xué)研究提供新線索,。
新聞公報說,，記錄生命遺傳信息的DNA呈穩(wěn)定的雙鏈螺旋結(jié)構(gòu),，但在復(fù)制,、轉(zhuǎn)錄和重組等過程中,，DNA鏈會出現(xiàn)一種超螺旋現(xiàn)象，這類似于螺旋狀的電話線在受到外力時可能出現(xiàn)復(fù)雜的螺旋狀態(tài),。
理化研究所的凌楓和柴田武彥等研究人員在酵母線粒體DNA的同源重組實驗中,，使用經(jīng)過高度純化的酶“Mhr1”進行催化，發(fā)現(xiàn)這種條件下的DNA同源重組不需要形成超螺旋,，而是通過一種名為“三鏈體”的中間體進行,。
凌楓對記者說,，曾有研究證明“Mhr1”酶在抑制線粒體異質(zhì)性上發(fā)揮著關(guān)鍵作用，此次研究揭示了其催化的反應(yīng)機制核心,。由于線粒體異質(zhì)性與衰老等生理過程密切相關(guān),，理化研究所的這項研究為抗衰老等方面的生物醫(yī)學(xué)研究提供了新線索。
這一研究成果將發(fā)表在5月號的美國《生物化學(xué)雜志》上,。(生物谷Bioon.com)
生物谷推薦原始出處：
J. Biol. Chem, 10.1074/jbc.M900023200
Heteroduplex joint formation free of net topological change by Mhr1, a mitochondrial recombinase
Feng Ling, Minoru Yoshida, and Takehiko Shibata
Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako-shi, Saitama 351-0198
Homologous pairing, an essential process for homologous recombination, is the formation of a heteroduplex joint by an invading single-stranded DNA (ssDNA) tail and a complementary sequence within double-stranded DNA (dsDNA). The base-rotation of the parental dsDNA, to switch from parental base-pairs to heteroduplex ones with the invading ssDNA, sterically requires vertical extension between adjacent base-pairs, which inevitably induces untwisting of the dsDNA. RecA is a prototype of the RecA/Rad51/Dmc1-family proteins, which promote ATP-dependent homologous pairing in homologous DNA recombination in vivo, except in mitochondria. As predicted by the requirement for the untwisting, dsDNA bound to RecA is extended and untwisted, and homologous pairing by RecA in vitro is extensively stimulated by the negative supercoils of dsDNA substrates. D-loop formation in negatively supercoiled dsDNA, which serves as an assay for homologous pairing, is also catalyzed in an ATP-independent manner by proteins structurally unrelated to RecA, such as Mhr1. Mhr1 is required for yeast mitochondrial DNA recombination instead of RecA-family proteins. Inconsistent with the topological requirements, tests for the effects of negative supercoils revealed that Mhr1 catalyzes homologous pairing with relaxed closed circular (cc) dsDNA much more efficiently than with negatively supercoiled dsDNA. Topological analyses indicated that neither the process nor the products of homologous pairing by Mhr1 involve a net topological change of cc-dsDNA. This would be favorable for homologous recombination in mitochondria, where dsDNA is unlikely to be under topological stress towards unwinding. We propose a novel topological mechanism wherein Mhr1 induces untwisting without net topological change.
