Cell Cycle 2 PDF

Cell cycle Cell cycle In eukaryotic cells, or cells with a nucleus, the stages of the cell cycle are divided into two major phases: interphase and the mitotic (M) phase. During interphase, the cell grows and makes a copy of its DNA. During the mitotic (M) phase, the cell separates it...

Cell cycle Cell cycle In eukaryotic cells, or cells with a nucleus, the stages of the cell cycle are divided into two major phases: interphase and the mitotic (M) phase. During interphase, the cell grows and makes a copy of its DNA. During the mitotic (M) phase, the cell separates its DNA into two sets and divides its cytoplasm, forming two new cells.  Eukaryotic cell cycle The cell cycle : events surrounding eukaryotic DNA replication and cell division (mitosis) are 1. G1 phase (Gap 1) : The period preceding replication 2. the S (synthesis) phase. DNA replication occurs 3. G2 phase, or Gap 2 before mitosis (M). 4. G0 phase: cells that have stopped dividing, such as mature T lymphocytes, are said to have gone out of the cell cycle. Such quiescent cells can be stimulated to reenter the G1 phase to resume division Cell division M phase G0 state G2 phase G1 phase S-phase (DNA synthesis cell cycle  DNA Synthesis Occurs During the S Phase of the Cell Cycle The cell regulates DNA synthesis by allowing it to occur only once per cell cycle, and only during S-phase, All eukaryotic cells have gene products that govern the transition from one phase of the cell cycle to another. Ø cyclins are a family of proteins whose concentration increases and decreases at specific times, that is, “cycle” during the cell cycle—thus their name. cyclin- dependent protein kinases  During the S phase, cells contain greater quantities of DNA polymerase and their expression drops following the synthetic phase until the reappearance of the signal for renewed DNA synthesis. ØDuring the S phase, the nuclear DNA is completely replicated once and only once. Øchromatin it is marked so as to prevent its further replication until it again passes through mitosis. This process is termed replication licensing.  The cell cycle is controlled at a series of “checkpoints” that prevent entry into the next phase of the cycle until the preceding phase has been completed. Ø Two key classes of proteins that control the progress of a cell through the cell cycle are : Ø the cyclins and Ø cyclin-dependent kinases (Cdks).  Cell cycle and Cell Cycle Checkpoints Mitosis (Cells Alive) These control the cell cycle. Ensure that each stage is completed properly before entering the next stage. G1 Checkpoint cell size S Checkpoint (DNA synthesis complete) G0 is where the cell G2 Checkpoint leaves the cell cycle. Cell size Differentiation DNA replication DNA damaged DNA damage M checkpoint Spindle assembly ØDuring interphase, the packing of the DNA molecule is less dense than it is in the condensed chromosome during metaphase. ØMetaphase chromosomes are nearly completely transcriptionally inactive CDK enzymes control the checkpoints A group of enzymes called kinases move the cell onto the next stage of the cell cycle Kinases bind to proteins called cyclins forming a CDK complex. (cyclin dependent kinase complex) They phosphorylate a checkpoint protein which activates it and allows the cell cycle to move on. Ø After they have done their job the checkpoint proteins are broken down by other enzymes. Cell moves forward through cell cycle (CDKs) that phosphorylate substrates essential for progression through the cell cycle Example : ØThe D cyclins activate CDK4 and CDK6. These two kinases are also synthesized during G1 in cells undergoing active division. § The D cyclins and CDK4 and CDK6 are nuclear Proteins that assemble as a complex in late G1 phase 1. One substrate for this kinase is the retinoblastoma (Rb) protein. 2. Rb it binds to and inactivates a transcription factor (E2F) necessary for the transcription of certain genes (histone genes, DNA replication proteins, etc) needed for progression from G1 to S phase. 3. The phosphorylation of Rb by CDK4 or CDK6 results in the release of E2F 4. thus, lead to gene transcription activation 5. and cell-cycle progression takes place. Many of the cancer-causing viruses (oncoviruses) and cancer-inducing genes (oncogenes) are capable of disrupting the apparent restriction that normally controls the entry of mammalian cells from G1 into the S phase. Øexcessive production of a cyclin, Øloss of a specific CDK inhibitor , Ø production or activation of a cyclin/CDK at an inappropriate time might result in abnormal or unrestrained cell division  Cancer can develop if there is damage in the checkpoints leading to uncontrolled cell division. Eg Over expression of the cyclin gene =too many cyclins being produced. Some cancer drugs are inhibitors of these CDK complexes. Increased levels of p53 activate transcription of genes that serve to inhibit the cell cycle p21, is capable of efficiently inhibiting the action of all CDKs. And thus the the cell cycle. Ø If DNA damage is too extensive to repair, the affected cells undergo apoptosis (programmed cell death) in a p53-dependent fashion. In this case, p53 induces the activation of a collection of genes that induce apoptosis. Ø Cells lacking functional p53 fail to undergo apoptosis in response to high levels of radiation or DNA-active chemotherapeutic agents. is one of the most frequently mutated genes in human cancers An example of the inhibitory effect of p53 on cell cycle progression. p21 inhibits cell cycle progression binding CDK/cyclin complexes or blocks DNA replication ØDNA, chromosome, and chromosome segregation integrity is continuously monitored throughout the cell cycle. Ø If DNA damage is detected in either the G1 or the G2 phase of the cell cycle, Ø if the genome is incompletely replicated, or if normal Øchromosome segregation machinery is incomplete (ie, a defective spindle), Ø cells will not progress through the phase of the cycle in which defects are detected. In some cases, if the damage cannot be repaired, such cells undergo programmed cell death (apoptosis).. Link the terms with the correct definition e.g. B2 1 Organelle in animal cells which produces the spindle A centriole 2 Chromosome pairs which are homologous B nucleolus Cell(s) produced as a result of 3 fertilisation C heterosomes 4 Dark staining area within the D histone nucleus 5 The chromosome pair which E zygote determines gender 6 Picture of the chromosomes from a F karyotype cell G homologous 7 Chromosomes with the same genes in the same location H autosomes Protein around which DNA strands 8 coil