法国巴黎-萨克莱高师法国国家科学研究中心生物与应用药理学实验室（LBPA, CNRS, ENS Paris-Saclay）

报告人简介：
Malcolm Buckle教授于1954年生于英国，于1980年在英国胡佛汉顿大学化学系获得博士学位，随后在加拿大安大略省汉密尔顿麦克马斯特大学健康科学生物化学系完成其博士后研究，现为法国巴黎-萨克莱高师法国国家科学研究中心（CNRS）生物及应用药理学实验室负责人。长期从事基因表达调控、染色质结构、生物传感、纳米粒子等生物化学、生物物理学领域的研究，并发展了多种相关研究技术。

报告摘要：
      We will describe an approach developed in our group that uses the probability of UV induced cyclobutane dimer formation between adjacent pyrimidines on the same DNA chain in naked and bound DNA as a probe of changes in local base structure not only between naked DNA and reconstituted nucleosomes but also at different stages of nucleosome formation. This technique of photo-chemical analysis of structural transitions (PhAST) induces photo-chemical alterations in DNA pyrimidine dimer formation. The location and intensities of these alterations are themselves affected by external agents that reshape the DNA structure and thus alter the photo-chemistry. Thus, the technique provides unique information on the local structure at a base level of the DNA.
      Gene expression is essentially controlled through the spatial and temporal distribution of nucleosomes on the genome. The presence of a nucleosome generally has an inhibitory effect on DNA binding proteins; indeed, the binding of TATA and the whole pol II transcription machinery requires the absence of nucleosomes. Nucleosomes are formed by histone octamers consisting of the heterodimer H2A/H2B and the tetramer H3/H4 wrapping ~147 base pairs of DNA ~1.7 times around them in a left-handed supercoil with an average radius of curvature of 9 nm.
      We will describe how we used PhAST to follow sequential changes in DNA that accompany nucleosome formation and to correlate these events with (a) changes in local parameters (essentially roll and twist) in the DNA and (b) coordinated Interactions with dimer, tetramer and hexamer subunits of histones. For the first time we are able to follow dynamic changes at a molecular level in DNA during nucleosome formation.

联 系 人：李明研究员（电话：8264 9058）