Molecular BiologyHongyun Yu2010.3.4,Lecturer: 俞红云 Room: 427 Tel: 3600937 E-Mail: ,TA: 龚德顺 Tel: 138 6672 4424 E-mail: ,Lecturer: 涂晓明 Room: 440A Tel: 3600757 E-Mail: ,课程安排： 按大纲顺序进行 考试：平时作业及课堂测验 2530 期末考试 7075。 教材： Essentials iGenetics by Peter J. Russell 参考书： 1. Molecular Biology of the Gene 5thed by Watson et al Pearson publication 2. Molecular Biology by Robert F. Weaver 3. Genetics by Peter J. Russell 4. Gene VIII,Molecular Biology Class Background Survey,遗传物质应该具有的基本特征是什么？ 双链DNA的基本结构特征是什么？ 真核生物染色体是由哪几部分组成的？ 什么是等位基因？ 什么是隐性突变？ 当我们说一个基因的某一种突变是隐性致死突变应该有什么依据（表型）？ 什么是蛋白质的结构域？有什么特点？,Genetics,Understanding the biological properties that are transmitted from parents to offsprings. The Subjects of Genetics: 1) Phenomenology of heredity 2) How gene control metabolism chromosome proteins; and RNA Euchromatin: less condensed, active Heterochromatin: highly condensed, inactive,Human Male Metaphase Chromosome arranged as a karyotype,Chromosome associating proteins,Histones: small basic proteins (+) 25% Lys +Arg, conservative H1: H1 has a central conserved core, the flanking regions are less conservative more than one kind in a cell H2A, H2B, H3, H4: very conservative A Chromatin contains equal weight of DNA and histone proteins,Chromosome associating proteins,Non-histones: All the other associating proteins beside Histone Acidic(-), varies from cell to cell, from time to time Large varity: Structural Histone gene of some species; and multi-gene family(-globin) Highly repetitive sequences: simple、short (1-10bp) 、thousands of copies: telomeres/centromeres/ satellite DNA, may have unusual %GC content. Centromere sequence: 8% in mouse. 50% in kangroo 5% in human,Highly repetitive satellite DNA,Microsatellite DNA: 2-4 bp repeates,Minisatellite DNA: 5- a few tens of bp repeates,Dispersed repeated sequences,1) Gene sequences: low copy number (50) histones; transposons; multigene family 2) Non-gene sequences: high copy number, up to one million, SINE/ LINE.,Non-gene sequences,Short interspersed repeats(SINE): 100-500 bp units (Alu I) Use as markers for genome analysis Long interspersed repeats (LINE): 5000bp or longer units. Transposons? FUNCTION? Unknown. Gene evolution?,Centromeres and Telomeres Mostly heterochromatic,Centromeres: the sites at which chromosomes attach to the mitotic and meiotic spindles. Sequences are conserved to some extent Telomeres: the ends of the chromosomes All telomeres in a given species share a common sequence,Centromeres,Responsibe for the accurate segregation of the replicated chromosomes to the daughter cells Consequences of nondisjunction: the zygotes mostly die some lives to produce abnormal offspring trisomy 21,Centromeres,Centromere sequences are not random There are proteins facilitating spindle fiber attachment to the centromere: Kinetochore,Centromeres of yeast,Kinetochore of Yeast,CDE: Centromere DNA elements CBF: Centromere binding factor,Functions of Telomeres,1. Prevent exonuclease from degrading chromosomes of the linear DNA ends 2. Prevent chromosome ends fusion 3. Facilitate replication at the ends without losing DNA material. Required for replication and stability of chromosome,What happens when chromosome broke?,A broken chromosome may have a sticky ends, which will cause two sticky ends to fuse-resulting one fused chromosome have two or none centromeres and cause problem in mitosis and meiosis.,Telomere sequences,Simple telomere sequences: Simple tandemly repeated, species-specific, at the very end of the chromosome molecule Telomere-associated sequences: Repeated but still complex sequences, extending thousands of base pairs in from telomere end.,Telomere sequences of yeast,How should this sticky end be protected?,T-loop at the end of chromosome,Electron micrograph of a T loop at the end of a chromosome isolated from a mouse hepatocyte. The bar at the bottom of the micrograph represents a length of 5,000 bp,5,000 bp,