overview of the cell cycle

cell cycle : A cell reproduces by performing an orderly sequence of events in which it duplicates its contents and then divides in two. (Cycle of duplication and division)

The most fundamental task in one cell cycle: the passing on of its genetic information to the next generation of cells

The duration of the cell cycle varies greatly from one cell type to another.
不同细胞的细胞周期时长差异巨大

M-phase里分为mitosis和cytokineses
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如果环境不适应,细胞可以停在G1期或进入G0期,环境合适时候会通过start/resriction point,开始DNA复制
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研究细胞周期的方法

  1. Observe living cells with a microscope
  2. Staining cells with special dyes or with antibodies that recognize specific cell components
    给细胞染色,比如DNA染色,微管染色
  3. Analysis of DNA content by the use of DNA-binding dye (Hoechst 33342)and a
    flow cytometer
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the cell cycle control system

The Cell-Cycle Control System Triggers the Major Events of the Cell Cycle

cell-cycle contron system 基于一系列的 biochemical switches,每个开关触发一个细胞周期中的事件

In most eukaryotic cells, the cell-cycle control system governs管理 cell-cycle progression at three major regulatory transitions过渡

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Cdks

The Cell-Cycle Control System Depends on Cyclically Activated Cyclin-Dependent Protein Kinases (Cdks)
周期蛋白依赖性蛋白激酶

cdks结合cyclins周期蛋白,形成复合体,然后催化细胞周期中的关键事件
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cyclins

The most important Cdk regulators.

Bounding tightly to a cyclin is a prerequisite先决条件 of the activation of Cdks.

Cyclins undergo a cycle of synthesis and degradation in each cell cycle.

不同周期蛋白含量的变化会导致不同的周期蛋白去结合cdks

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图中的三种cyclins是所有真核细胞必须的,还有一种是G1-cyclin

cdk被激活的结构图👇

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抑制cdk

通过inhibitory phosphorylation抑制👇
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通过cdk inhibitor protein(CKIs)抑制👇
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Metaphase to Anaphase分裂中期到分裂后期

这部分估计不考

Regulated Proteolysis蛋白水解 Triggers the Metaphase-to-Anaphase Transition

Progression through the metaphase- to-anaphase transition is triggered by protein destruction

APC/C 催化加速cdk-M-cyclin水解👇
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APC/C 激活separase,separase催化姐妹染色单体分开👇
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还有一种东西叫SCF,在G1后期专门泛素化CKI促进降解,帮助激活S-cdk并开始DNA复制
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总结

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S phase

复制一次

G1会形成preRC,授权复制起点,到了S期会激活DNA解旋酶,复制一次之后的复制起点没有preRC,没有被授权,这样就控制了S期DNA只复制一次👇
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姐妹单体不分开

Sister-chromatid cohesion depends on a large protein complex called cohesion.
姐妹染色单体的黏连依赖于一种称为黏连蛋白的大型蛋白质复合体

在S期DNA复制时,黏连蛋白会在每条姐妹染色单体的长度上多个位置沉积

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mitosis

prophase, prometaphase, metaphase, anaphase, and telophase
前期、前中期、中期、后期和末期

主要分成两部分

  1. M-cdk trigger G2/M transition,发生前期,前中期和中期的过程
  2. APC/C trigger metaphase-to-anaphase transition,发生中期到后期的过程

M-cdk突增👇
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原理是正反馈调节👇
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prophase前期

1.形成染色体

Condensin Helps Configure Duplicated Chromosomes for Separation
凝缩蛋白帮助配置复制的染色体以进行分离

细胞在早期有丝分裂中投入大量能量,逐渐将姐妹染色单体重新组织成相对较短、独特的结构,以便在后期更容易被拉开

  1. chromosome condensation : the chromatids are dramatically compacted
  2. sister-chromatid resolution : the two sisters are resolved into distinct, separable units

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2.mitotic spindle 纺锤体

based on microtubule

responsible for the central event of mitosis——chromosome segregation

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在prophase开始形成

4种纺锤体形成和发挥功能需要的motor protein↓ kinesin-5, kinesin-14, kinesins-4/10, and dynein
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3.centrosome 中心体

中心体在细胞周期的前期开始复制,到M期就有两个完整的中心体
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prometaphase前中期

1.Nuclear-Envelope Breakdown

The Completion of Spindle Assembly in Animal Cells Requires Nuclear-Envelope Breakdown

M-Cdk phosphorylates nuclear pore complexs and lamins
M-Cdk 磷酸化核孔复合体和核纤层蛋白

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2.Mitotic Chromosomes Promote Bipolar Spindle Assembly

有丝分裂染色体促进双极纺锤体的组装

染色体结合GEF激活一个GTPase Ran,Ran能释放microtubule-stabilizing proteins

3.Kinetochores Attach Sister Chromatids to the Spindle

动粒将姐妹染色单体连接到纺锤体上

动粒是 a giant, multilayered protein structure that is built at the centromeric
region of the chromatid
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连接依赖Ndc80 complex👇
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Bi-orientation Is Achieved by Trial and Error
如果不是两端各连一个那么tension不够,就会断开👇
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断开机理👇Aurora-B kinase会催化连接断开
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metaphase中期

1.spindle assembly checkpoint

Unattached Chromosomes Block Sister-Chromatid Separation

有一个检查点,所有姐妹染色体都正确连接前不会开始分离

2.metaphase plate

在三种力作用下染色体排到赤道板上

  1. protein at the kinetochore
    动粒上的蛋白质产生的力将动粒及其相关的染色单体沿着动粒微管拉向纺锤体极
  2. microtubule flux
    微管本身被拉向纺锤体极并在其负端拆解
  3. polar ejection force

anaphase后期

APC/C启动后期

拉开姐妹染色单体

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telophase末期

1.纺锤体解体

2.成核

Segregated Chromosomes Are Packaged in Daughter Nuclei at anaphase
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cytokinesis

the division of the cytoplasm in two
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Actin and Myosin II in the Contractile Ring收缩环 Generate the Force for Cytokinesis

The Microtubules of the Mitotic Spindle Determine the Plane of Animal Cell Division
微管与纺锤体决定动物细胞分裂的平面