细胞周期和分裂

1、细胞周期和分裂Cell cycle phases:Interphase: G1-S-G2M phase: Mitosis, CytokinesisPurpose of the cell cycle studyS SG G2 2M MG G1 1CytokinesisS SG G2 2M MG G1 1基因组复制基因组复制GENOME DUPLICATION细胞分裂细胞分裂CELL DIVISION限制点限制点/ /检控点检控点RESTRICTION POINT纺锤体组装纺锤体组装SPINDLE ASSEMBLY细胞核重建细胞核重建/ /细胞生长细胞生长NUCLEAR REASSEMBLY/CE

2、LL GROWTHG2期检控点期检控点G2 CHECKPOINTCDKKinases1. A typical Cell CycleFigure 17-14 Molecular Biology of the Cell ( Garland Science 2008)Types of the cell cycle 高等动物体细胞的细胞周期高等动物体细胞的细胞周期Courtesy of Sodmergen高等植物体细胞的细胞周期高等植物体细胞的细胞周期芽生酵母芽生酵母（S. cereviciae) 的细胞周期的细胞周期裂殖酵母裂殖酵母（S. pombe) 的细胞周期的细胞周期早期胚胎细胞的细胞周期早期

3、胚胎细胞的细胞周期Oocyte growth and egg cleavage in XenopusMolecular Biology of the Cell ( Garland Science 2008)动物早期胚胎细胞的细胞周期（动物早期胚胎细胞的细胞周期（2 2）细菌的细胞周期细菌的细胞周期体细胞和胚胎细胞的细胞周期比较体细胞和胚胎细胞的细胞周期比较Figure 17-11 Molecular Biology of the Cell ( Garland Science 2008)Figure 17-12 Molecular Biology of the Cell ( Garland Sc

4、ience 2008)Symmetric and asymmetric cell division细胞不对称分裂是生物个体发育的基础细胞不对称分裂是生物个体发育的基础Gnczy, P. NRMCB 9, 355-366, 2008Cell cycle synchronization Cell cycle synchronization：M phase Cell cycle synchronization：S phaseCell Division:mitosisCell DivisionThe Nuclear Envelope Breakdown(1) Prophase to Prometaph

5、ase(1) ProphaseActivated M-Cdk phosphrylates condensin subunits, triggering the assembly of condensin complexes on DNA and condensation of the chromosome. The condensin can use energy of ATP hydrolysis to promote DNA coiling (in vitro).The sister chromatids are glued together by multisubunit protein

6、 complex called cohesins.The chromatin condensation to mitotic chromosomes(2) MetaphaseAll chromosomes align at metaphase plate Microtubules are highly dynamic in the metaphase spindle.Assembly of kinetochore at the end of prophaseGolgi, ER etc. disperse to form vesicles; kinetochore assemblySchemat

7、ic representation of the kinetochorevSpindle MTs capture chromosomes Targeting of preassembled acentrosomal TACC3-microtubule seeds/asters to kinetochore facilitates kinetochore capture by centrosomal microtubules.Fu et al, 2013. PNASA unique model for kinetochore capture by microtubules duringmitot

8、ic spindle assembly in somatic cells with centrosomes.Fu et al, 2013. PNASPhosphorylation of Crm1 by CDK1cyclin-B promotesRan-dependent mitotic spindle assemblyA model for the role of Crm1 and its phosphorylation by CDK1cyclin-B in the regulation of the mitotic spindle assembly Wu et al, 2013. J. Ce

9、ll Sci.Two alternative models of how the kinetochore may generate a poleward force on its chromosome during anaphase A.纺锤体组装过程纺锤体组装过程染色体整列染色体整列A. A. 细胞分裂前期和前中期，细胞分裂前期和前中期，Mad Mad 和和Bub Bub 蛋白在染色体的动粒上聚蛋白在染色体的动粒上聚集。集。B. B. 微管与动粒联结后，微管与动粒联结后，Mad Mad 和和Bub Bub 蛋白消失，某些染色体滞后蛋白消失，某些染色体滞后，未与微管联结的动粒依然含有，未与微管

10、联结的动粒依然含有Mad Mad 和和Bub Bub 蛋白。蛋白。C. C. 所有染色体的动粒均与微管所有染色体的动粒均与微管联结，联结，Mad Mad 和和Bub Bub 蛋白消失，染蛋白消失，染色体列队到赤道板色体列队到赤道板。解释染色体在赤道面整列的两种假说The spindle checkpoint(mammalian cell in late prometaphase labeled with anibodies against the spindle checkpoint protein Mad2 and tubulin). Mad2The spindle-attachment c

11、heckpoint: Anaphase is delayed until all chromosoms are positioned at the metaphase plate“The spindle assembly checkpoint works like a rheostat rather than a toggle switch”. The spindle assembly checkpoint (SAC) is essential in mammalian mitosis to ensure the equal segregation of sister chromatids.

12、The SAC generates a mitotic checkpoint complex (MCC) to prevent the anaphase-promoting complex/cyclosome (APC/C) from targeting key mitotic regulators for destruction until all of the chromosomes have attached to the mitotic apparatus. A single unattached kinetochore can delay anaphase for several h

13、ours, but how it is able to block the APC/C throughout the cell is not understood. Present concepts of the SAC posit that either it exhibits an all-or-nothing response or there is a minimum threshold sufficient to block the APC/C . Here, we have used gene targeting to measure SAC activity, and find

14、that it does not have an all-or-nothing response. Instead, the strength of the SAC depends on the amount of MAD2 recruited to kinetochores and on the amount of MCC formed. Furthermore, we show that different drugs activate the SAC to different extents, which may be relevant to their efficacy in chem

15、otherapy.J Pines, 2013. NCBv The events of Anaphase: Both anaphase A and anaphase B contribute to the movement of chromosome toward the spindle polesAnaphase A: The movement of the chromosomes toward the poles; Kinetochore MT disaassenble at both ends during anaphase A.Anaphase B: The two spindle po

16、les move farther apart. Both pushing and pulling forces contribute to anaphase B(3) AnaphaseAnaphase inAnimal cells Anaphase in plant cellsThe chromatin separationAnaphase B: The two spindle poles move farther apart.The sliding of overlap MT at anaphase.MetaphaseLate anaphase(4) Telophase Chromosome

17、 decondenses Nuclear envelope reforms around individual chromosomes Golgi, ER ,etc. reconstruct Nucleolus reassemblesMitosis endsTelophaseAnaphase in plant cells(5) Cytokinesis(a) In animal cells The MT of mitotic spindle determine the plane of animal cell division; Mitosis can occur without cytokin

18、esis. 动物细胞动物细胞胞质分裂胞质分裂Figure 17-50b Molecular Biology of the Cell ( Garland Science 2008)Figure 17-50c Molecular Biology of the Cell ( Garland Science 2008)Contractile ring: Actin and myosinII in the contractile ring generate the force for cytokinesisA. 中央纺锤体发出的信号决定分裂沟的定位。B. 接近分裂沟位置的纺锤体微管发出信号，促进分裂沟的形成。C. 远离分裂沟位置的星体微管发出抑制性信号 (T 形箭头)，抑制远离分裂沟端部的细