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| Frage | Antworten |
| The purpose of the cell cycle: why cells need to divide | - to copy the genome and partition copies equally between daughter cells in order to continue the species - for growth - to maintain the total cell number in adult organisms; replacing lost/damaged cells. |
| Prokaryote cell division: Binary fission | Prokaryotes consist of a cell membrane surrounded by a cell wall w/circular DNA inside, attached to the membrane, Binary fission: 1. cell enlarges, DNA duplicates 2. septum forms; DNA in each section 3. cells separate, base sequence maintained. 2 pathways need to be coordinated: - the replication of DNA (and partition of copies) - cytokenesis (cell seperation) |
| Cell division in prokaryotes: 1. replication of DNA | - circular chromosomes of prokaryotes have one origin of replication (ori). - the beginning of DNA replication is sequence-specific. 1. replication fork begins: - DNA unwinds, 2 replication forks form at the origin, copy bases using DNA polymerase down each fork, meaning replication is bidirectional. 2. when both forks have been replicated, 2 identical copies of the circular chromosome remain; 1 old strand and 1 new strand- retaining base sequences. |
| Cell division in prokaryotes: 2. cytokenesis | - cytokenisis is principally controlled by a protein in bacteria called FrsZ, which is distributed randomly throughout the cytoplasm of the cell. 1. when cytokenesis is instructed to take place, FtsZ forms a ring of protein in the inner cytoplasmic membrane at the future division site. 2. this protein 'ring' then contracts, bringing the membranes together until they fuse and the cell splits into 2. The protein ring then disaggregates and FtsZ is distributed evenly in the new cell. - these 2 pathways are coordinated- |
| Cell division in prokaryotes: multifork replication explained | Cell cycle of groeing bacteria FtsZ is shorter than the time needed to copy DNA: - cell division takes place every 20 mins, while DNA replication takes 40. - this paradox is solved by multifork replication; DNA replication is initiated BEFORE completion of the previous round. - this ensures that at least one round of replication is finished before cytokenesis, ensuring ALL daughter genes contain a copy of the gene. |
| Eukaryotic cell cycle: additional complications introduced by the eukarotic cell cycle compared to prokaryotes | 1. the genome is composed of multiple linear chromosomes (which requires co-cordinated replication of them all, as well as their segregation) 2. multicellularity- cells in the context of organs and tissues 3. numerous organelles- must partition into daughter cells- |
| Characteristics of the eukaryotic cell cycle | - details vary between organisms and life stages but some characteristics are universal: - that DNA must be faithfully replicated and the base sequence has to be conserved- mistakes in this lead to evolution and cancer - replicated chromosomes must be accurately segregated |
| The 4 phases of the eukaryotic cell cycle: G1: growth phase | G1- growth phase: - Mass of organelles and protein doubles , including synthesis of enzymes that drive DNA replication - this occurs during the gap between the end of the last cell cycle and the beginning of a new one. |
| S: DNA synthesis phase | - chromosome duplicates 46 chromosomes to 92 chromosomes - at the end of this phase, each replicated chromosome consists of a pair of identical sister chromatids. These do not seperate from one another, else it would be hard to acheive bipolar attachment to mitotic spindle. - cohesion ensures these sister chromatids do not drift apart. Composed of SMC proteins (Structural maintenence of chromosomes) |
| G2: 2nd growth phase | Growth phase 2: interval between the end of the S phase and the beginning of the M phase. - cell monitors the internal and external enviroments to ensure that conditions are suitable. - ensures preparations are complete. - together, G1 and G2 phases provide additional time to prepare. |
| M phase | - Mitotic phase; 1. duplicated chromosomes condense and become visible 2. formation of mitotic spindle; bipolar array of microtubules. Kinetochore- complex of proteins attached to the centromere. 3. nuclear membrane must breakdown early in mitosis so the spindle has access to chromosomes. |
| Cytokinesis | - the end of the cell cycle; occurs once sister chromatids have reached opposite sides of the cell. - Actin and myosin filaments of contractile ring contract and pinch the cell into 2, giving 2 daughter cells, each with their own nucleus. - nuclear membranes then reform around each cell - cytoplasm is divided into 2 by actin/myosin II contractions |
| Diffences in cytokenesis between plants and animals | In animal cells the contratile ring divides cytoplasm from the outside in, whereas in plants there is no contractile ring. Instead, a new cell wall is constructed between the daughter nuclei, so the cytoplasm is partitioned from the inside out. - this is guided by the phragmoplast, which contains microtubules derived from the mitotic spindle. - golgi-derived vesicles travel on these microtubules to provide phragmoplasts with materials to make the cell wall. |
| Variations in cell cycle between different cell types. | - Timing eg: an early frog embryo takes 30 mins to divide, whereas human liver cells take a year - Nuclear envelope dynamics eg: closed vs open mitosis. closed (where membrane remains intact: yeast) open (where spindle is outside so has to breakdown: human cells). - Early embryonic cycle: no growth 'G' phases, divides without growing as egg divides up. - Polarity- some proteins are divided aysmmetrically; where not all proteins are in each daughter cell. This determines what kind of cell it will differentiate into and is determined by polarity. - Stem cells- undifferentiated cells that differentiate when they divide, unless they are attached to niche cells. |
| Other aspects of cell cycle control | - anchorage dependence- cells must be attached to a substratum in order to divide- except from cancer cells. - density dependent inhibition- cells stop dividing when they contact each other eg liver gets bigger until it reaches the edges- except in cancer cells. |
| The cell cycle control system: overview | 1. Cell cycle engine- simple protein complex that drives the cell cycle 2. Co-ordination- replicated DNA must go through mitosis before replication occurs again 3. Checkpoints- stop cycle if cell is deprived of nutrients or DNA is damaged or if chromosomes fail to attach to spindle. |
| The cell cycle control system: Cell cycle engine | - phases of the cell cycle are driven by the action of the protein kinase cyclin dependent protein kinase (CDK). - the levels of the CDK remain constant throughout the cell cycle, it is it's activity that changes. - CDK is only active when it is complexed with the protein cyclin. - there are different CDKs, each protein-CDK complex activate a different phase of the cell cycle. - EG mitotic CDK phosphorylates nuclear lamin, causing their depolarisation, triggering the nuclear membrane breakdown. |
| The cell cycle control system: co-ordination | - the cell cycle is tightly regulated- phases must occur in the proper order. - the S and M phases must occur only once in each cell cycle- so a mechanism must exist to prevent replication of G2 DNA. - S phase cell fuses with a G1 phase cell; the S phase nucleus continues DNA replication. |
| The cell cycle control system: Checkpoints | Checkpoints are surveillance mechanisms that operate continually to ensure the next phase is not initiated until the previous one has been completed. 1. Restriction checkpoint 'R' in G1 a positive signal in the form of growth factor from the outside instructs the cell to divide. 2. At G2 DNA synthesis should be complete, checkpoint here decides if cycle can move on, or if cell cycle should be suspended. 3. Spindle checkpoint- Ensures that every chromosome is attached to the spindle. If this is not the case then the cell cycle is suspended 4. DNA damage checkpoint- operates throughout the cycle, arrests the cycle if damage is detected. |
| Consequences of checkpoint failiure | - Failiure of DNA damage checkpoint: If the cell cycle continues despite damage, mutations accumulate, which can result in cancer. - Failiure of spindle checkpoint |
| Cancer and the cell cycle | - all cancers feature a de-regulated cell cycle as a consequence of mutation - In cancer, signals that start/stop the cell cycle are ignored - checkpoints that protect the genome no longer operate - cells do not communicate with one another |
| Summary | - In the prokaryotic cell cycle, multifork replication compensates for the mismatch in timing between DNA replication and cell division. - the eukaryotic cell cycle is divides up into 4 phases, enabling faithful replication and segregation of chromosomes. - The cyclin-dependent kinase/cyclin complex drives the eukaryotic cell cycle - the cycle is subject to regulation at many levels, inc checkpoints that guard against accumulation of mutations and missegregation of chromosomes. |
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