日本理化研究所日前发表新闻公报说，该所研究人员发现酵母线粒体中的DNA（脱氧核糖核酸）在一定条件下进行同源重组时，不像以前认为的那样需要DNA形成超螺旋。这一发现将为抗衰老等方面的生物医学研究提供新线索。 新闻公报说，记录生命遗传信息的DNA呈稳定的双链螺旋结构，但在复制、转录和重组等过程中，DNA链会出现一种超螺旋现象，这类似于螺旋状的电话线在受到外力时可能出现复杂的螺旋状态。 理化研究所的凌枫和柴田武彦等研究人员在酵母线粒体DNA的同源重组实验中，使用经过高度纯化的酶“Mhr1”进行催化，发现这种条件下的DNA同源重组不需要形成超螺旋，而是通过一种名为“三链体”的中间体进行。 凌枫对记者说，曾有研究证明“Mhr1”酶在抑制线粒体异质性上发挥着关键作用，此次研究揭示了其催化的反应机制核心。由于线粒体异质性与衰老等生理过程密切相关，理化研究所的这项研究为抗衰老等方面的生物医学研究提供了新线索。 这一研究成果将发表在5月号的美国《生物化学杂志》（JBC）上。（来源：新华网 钱铮） （《生物化学杂志》（JBC） ，DOI: 10.1074/jbc.M900023200，Feng Ling，Takehiko Shibata） 更多阅读（英文） JBC发表论文摘要 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 Corresponding Author: ling@postman.riken.go.jp 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.

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