細(xì)胞周期和分裂

1、細(xì)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基因組復(fù)制基因組復(fù)制GENOME DUPLICATION細(xì)胞分裂細(xì)胞分裂CELL DIVISION限制點(diǎn)限制點(diǎn)/ /檢控點(diǎn)檢控點(diǎn)RESTRICTION POINT紡錘體組裝紡錘體組裝SPINDLE ASSEMBLY細(xì)胞核重建細(xì)胞核重建/ /細(xì)胞生長細(xì)胞生長NUCLEAR REASSEMBLY/CE

2、LL GROWTHG2期檢控點(diǎn)期檢控點(diǎn)G2 CHECKPOINTCDKKinases1. A typical Cell CycleFigure 17-14 Molecular Biology of the Cell ( Garland Science 2008)Types of the cell cycle 高等動物體細(xì)胞的細(xì)胞周期高等動物體細(xì)胞的細(xì)胞周期Courtesy of Sodmergen高等植物體細(xì)胞的細(xì)胞周期高等植物體細(xì)胞的細(xì)胞周期芽生酵母芽生酵母（S. cereviciae) 的細(xì)胞周期的細(xì)胞周期裂殖酵母裂殖酵母（S. pombe) 的細(xì)胞周期的細(xì)胞周期早期胚胎細(xì)胞的細(xì)胞周期早期

3、胚胎細(xì)胞的細(xì)胞周期Oocyte growth and egg cleavage in XenopusMolecular Biology of the Cell ( Garland Science 2008)動物早期胚胎細(xì)胞的細(xì)胞周期（動物早期胚胎細(xì)胞的細(xì)胞周期（2 2）細(xì)菌的細(xì)胞周期細(xì)菌的細(xì)胞周期體細(xì)胞和胚胎細(xì)胞的細(xì)胞周期比較體細(xì)胞和胚胎細(xì)胞的細(xì)胞周期比較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細(xì)胞不對稱分裂是生物個體發(fā)育的基礎(chǔ)細(xì)胞不對稱分裂是生物個體發(fā)育的基礎(chǔ)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.紡錘體組裝過程紡錘體組裝過程染色體整列染色體整列A. A. 細(xì)胞分裂前期和前中期，細(xì)胞分裂前期和前中期，Mad Mad 和和Bub Bub 蛋白在染色體的動粒上聚蛋白在染色體的動粒上聚集。集。B. B. 微管與動粒聯(lián)結(jié)后，微管與動粒聯(lián)結(jié)后，Mad Mad 和和Bub Bub 蛋白消失，某些染色體滯后蛋白消失，某些染色體滯后，未與微管聯(lián)結(jié)的動粒依然含有，未與微管

10、聯(lián)結(jié)的動粒依然含有Mad Mad 和和Bub Bub 蛋白。蛋白。C. C. 所有染色體的動粒均與微管所有染色體的動粒均與微管聯(lián)結(jié)，聯(lián)結(jié)，Mad Mad 和和Bub Bub 蛋白消失，染蛋白消失，染色體列隊(duì)到赤道板色體列隊(duì)到赤道板。解釋染色體在赤道面整列的兩種假說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. 動物細(xì)胞動物細(xì)胞胞質(zhì)分裂胞質(zhì)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. 中央紡錘體發(fā)出的信號決定分裂溝的定位。B. 接近分裂溝位置的紡錘體微管發(fā)出信號，促進(jìn)分裂溝的形成。C. 遠(yuǎn)離分裂溝位置的星體微管發(fā)出抑制性信號 (T 形箭頭)，抑制遠(yuǎn)離分裂溝端部的細(xì)