The Cell Cycle and Its Control PJ1311 PDF

The Human Body PJ1311 The Cell Cycle and Its Control Dr Lamia Kandil Lecturer of Pharmacy Practice ,PhD,FHEA MB138 [email protected] vevox.app ID: 102-353-245 Kandil Lectures We will be covering 3 lectures on Genomics 1. Introduction to...

The Human Body PJ1311 The Cell Cycle and Its Control Dr Lamia Kandil Lecturer of Pharmacy Practice ,PhD,FHEA MB138 [email protected] vevox.app ID: 102-353-245 Kandil Lectures We will be covering 3 lectures on Genomics 1. Introduction to Genomics 2. The central dogma of life (Transcription ,Translation) 3. Cell cycle and control mechanism The cell cycle What is the cell cycle? All cells are derived from pre-existing cells Cell cycle: ordered sequences of events that occurs in the cell in preparation of cell division The Cell cycle has two basic Function :  Copying cellular components and DNA duplication  Dividing the cell so that components are distributed evenly to the daughter cells The alternating “growth” and “division” activities of the cell is called the “cell cycle”. Cell division is an integral part of the cell cycle.  Cell cycle Two identical daughter cells Parent Cell  Why the cell division occur? In unicellular organisms, division of one cell reproduces the entire organism (reproduction) Multicellular organisms depend on cell division for Growth (increase in numbers) and maintained and repaired (adults renewal e.g. liver, skin). Are all cells divide? NO some cell can’t divide e.g eye lens, nerve cell, heart cells. Theses cells maintained and  What is the cell cycle basic function? The “growth” activity corresponds to “Interphase”. cell growth and copying of chromosomes in preparation for cell division  The division activity corresponds to “M (mitosis and cytokinesis) phase”. Interphase M Interphase M Interphase G1 S G2 M G1 S G2 M G1 S G2 Stages of the cell cycle  Stages of the cell cycle State Description Abbreviation Quiescent/ Resting phase where cell has left cycle & Gap 0 G0 Senescent has stopped dividing Cells increase in size in Gap 1. G1 Gap 1 G1 checkpoint control mechanism ensures that everything is ready for DNA synthesis Synthesis S DNA replication occurs during this phase Interphase During gap between DNA synthesis & mitosis, cell will continue to grow. G2 Gap 2 G2 checkpoint control mechanism ensures that everything is ready to enter M (mitosis) phase & divide Cell growth stops at this stage & cellular energy is focused on orderly division into Cell Mitosis M two daughter cells. checkpoint in middle of division mitosis (Metaphase Checkpoint) ensures that cell is ready to complete cell division  Interphase  Interphase (about 90% of the cell cycle) is span between cell division can be divided into subphases  G1 phase (“first gap”) the cell size increased  S phase (“synthesis”) chromosomes are duplicated (longest phase)  G2 phase (“second gap”) cell prepared to divide Watch this https://www.bing.com/videos/riverview/relatedvideo?q=CELL% 20CYCLE%20CYCLIN%20REGULATION%20control%20system& mid=0A47F70DC695DE8F7F410A47F70DC695DE8F7F41&ajax hist=0 © 2011 Pearson Education, Inc.  Interphase: G1 Events during G1 1 stage of Cell growth after cell division of chromosomes for replication Preparation  st  Duplication of cellular components (cytoplasm and organel)  Cell carries on its normal metabolic activities  G1 checkpoint (or restriction point); cell commits to division or exits from cell cycle  S- phase Original DNA strand  The instructions for making cell parts are encoded in the DNA, so each new cell must get a complete set of the DNA molecules  DNA must be copied or replicated before cell division  Each new cell will then have an identical copy of the DNA Two new, identical DNA strands 1  DNA Replication semiconservative Watson and Crick base pairing maintained Synthesis in 5’ to 3’ direction A primer is needed for initiation a complex process involving several enzymes and proteins (Replisome) https://www.youtube.com/watch?v=TNKWgcFPHqw Copying DNA Replication of DNA ◆ base pairing allows each strand to serve as a template for a new strand Proteins and Enzymes  General features of DNA replication DNA replication is semi conservative It is bidirectional process It proceed from a specific point called origin It proceed in 5’-3’ direction It occur with high degree of fidelity It is a multi-enzymatic process  Knowing the structure of DNA, scientists speculated and then proved that DNA is the template for copying the genetic code. See how information in DNA is copied to make new DNA molecules. https://www.youtube.com/watch?v=I9ArIJWYZHI https://www.youtube.com/watch?v=TNKWgcFPHqw DNA replication occurs by three steps 1. Initiation: 2. Elongation: *Leading strand synthesis *Lagging strand synthesis 3. Termination  S- phase  Duplicated chromosomes are called chromatids  & are held together by the centromere Called Sister 1  S- phase  DNA replication  Duplication of the centrosome  The centrosome is located near the nucleus of the cell and contains the microtubule organizing center MTOC in animal cells. It contains two centrioles surrounding by loose collection of protein that migrate to the poles before cell division and serve to organize the spindle.  Chromosomal Chromosomes DNA molecules 1 Centromere Chromosome arm  Chromosomal Chromosomes DNA molecules 1 Centromere Chromosome arm Chromosome duplication (including DNA replication) and condensation 2 Sister chromatids  Chromosomal Chromosomes DNA molecules 1 Centromere Chromosome arm Chromosome duplication (including DNA replication) and condensation 2 Sister chromatids Separation of sister chromatids into two chromosomes 3  Interphase: G2  2 nd Cell growth stage  Occurs after DNA has been copied  All cell structures needed for division are made (e.g. centrioles)  Both organelles & proteins are synthesized  Checkpoint for entry into M phase  Mphase Mitosis and cytokinesis together represent the fourth and final stage of the eukaryotic cell cycle, called the M phase Mitosis is process by which cell separates chromosomes in its cell nucleus into two identical sets in two nuclei: During process of mitosis pairs of chromosomes condense & attach to fibers that pull sister chromatids to opposite sides of cell, followed immediately by cytokinesis, which divides nuclei, cytoplasm, organelles & cell membrane into two cells containing roughly equal shares of these cellular components Phases of Mitosis Prophase 2 4 What the cell looks like What’s Kinetochor e kinetochore is a protein strucutre on chromatide where microtubules will bind to it in cell division to pull the two sister chromatide a part each sister chromatid has its own kinetochore (arise from centromer) sister chromatids become attached by their kinetochores to microtubules from opposite poles Used in cell division (mitosis & miosis)  Prometaphase(Late prophase)  Nuclear membrane & nucleolus are broken down  Chromosomes continue condensing & are clearly visible  Spindle fibers called kinetochores attach to the centromere of each chromosome  Spindle finishes forming between the poles of the cell  METAPHASE 1.Chromosomes chromosomes are highly condensed line up in the middle (meta phase plate) 2.Nuclear envelope is gone (no nucleus) 3.Spindle fibers (on opposite poles) are stretching towards the chromosomes 4-the mitosis checkpoint appears to be here; progress past metaphase is typically prevented until the kinetochores are all attached to microtubules Sketch The Spindle 2  Anaphase  Occurs rapidly  Sister chromatids are pulled apart to opposite poles of the cell by kinetochore fibers  the protein tethers at the centromere between the chromatids What’s are broken occurring  each former sister chromatid can now be called a chromosom 2  Telophase  prophase is essentially reversed  Sister chromatids at opposite poles  Spindle disassembles  Nuclear envelope forms around each set of sister chromatids and chromosome condensed  Nucleolus reappears and interphase cellular functions resume  https://www.youtube.com/watch?v=5bq 1To_RKEo  Cytokinesis Means division of the cytoplasm Divides the cell into two daughter cells (cytoplasm, organelles cytokinesis usually begins in telophase and ends shortly thereafter Cytokinesis (part of M phase, not part of mitosis) Cleavage furrow Daughter Cells of Mitosis  Have the same number of chromosomes as each other and as the parent cell from which they were formed  Identical to each other  Must grow in size to become mature cells (G1 of Interphase)  Ready to enter in new cell cycle PARENT CELLS  The Cell Cycle Control System  The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock  The cell cycle control system is regulated by both internal and external controls  The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received © 2011 Pearson Education, Inc.  G1 checkpoint Control S G1 system M G2 M checkpoint G2 checkpoint  G0 G1 checkpoint G1 G1 (a) Cell receives go-ahead (b) Cell does not receive a signal go-ahead signal Cancer cells do not respond normally to the body’s control mechanisms Cancer cells may not need growth factors to grow and divide  They may make their own growth factor  They may convey a growth factor’s signal without the presence of the growth factor  They may have an abnormal cell cycle control system  https://www.bing.com/videos/riverview/relatedvideo?&q=c yclin+and+cdk+in+cell+cycle+animation&&mid=334D01 31C5C47DB4D58C334D0131C5C47DB4D58C&&FORM=V RDGAR  Who is responsible for Progression through the cell cycle? 1.Cyclins * Definition: family of proteins that activate cyclin-dependent kinase (Cdk) enzymes * Include: cyclin A, cyclin B, cyclin D, cyclin E  2.Cyclin – dependent kinases * Definition: family of protein kinases have role in regulating cell cycle * Include: cdk1, cdk2, cdk4, cdk6 (Cyclin-Cdk Complex)  Cyclins Cyclin dependent kinases (cdks) Cdk4,6 G1 Cyclin D Cyclin E Cdk2 S Cyclin A Cyclin A Cdk1 M Cyclin B  Maturation Promoting Factor * Definition: heterodimeric protein composed of cyclin B & cyclin-dependent kinase (CDK1) * Function: promotes entrance into mitosis (M phase) from G2 phase by phosphorylating multiple proteins needed during mitosis  Cyclic fashion for the conc of Cyclins  Summary The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produce two genetically identical cells. The cell cycle has two major phases: interphase and the mitotic phase. Cell cycle control. There are internal control mechanisms that operate at three main cell cycle checkpoints at which the cell cycle can be stopped until conditions are favourable. These checkpoints occur near the end of G 1, at the G2–M transition, and during metaphase Cdks, cyclins are direct regulators of cell cycle transitions, but they aren’t always in the driver’s seat. Instead, they respond to cues from inside and outside the cell. These cues influence activity of the core regulators to determine whether the cell moves forward in the cell cycle. Positive cues, like growth factors, typically increase activity of Cdks and cyclins, while negative ones, like DNA damage, typically decrease or block activity. Important videos to watch https://www.youtube.com/watch?v=TNKWgcFPHqw https://www.youtube.com/watch?v=5bq1To_RKEo https://www.youtube.com/watch?v=NwwcWqL5hhI https://www.youtube.com/watch?v=Jmqd9Qj_PTA https://www.youtube.com/watch?v=nEMMKzYQf9A  Join: vevox.app ID: 102-353-245POLL What is the main purpose of the cell cycle in eukaryotic OPEN cells? 1. a) DNA replication 4.84% 2. b) Cell growth 20.97% 3. c) Cellular repair 6.45% ü 4. d) Cell division 67.74%  Join: vevox.app ID: 102-353-245POLL Which phase of the cell cycle is responsible for DNA OPEN replication? 1. a) G1 phase 6.67% 2. b) G2 phase 5% ü 3. c) S phase 86.67% 4. d) M phase 1.67%  Join: vevox.app ID: 102-353-245POLL During which phase of the cell cycle do chromosomes OPEN condense, and the nuclear envelope breaks down? 1. a) G1 phase 1.67% 2. b) G2 phase 0% ü 3. c) Prophase 95% 4. d) Anaphase 3.33%  Join: vevox.app ID: 102-353-245POLL Which molecule is responsible for phosphorylating target OPEN proteins in the cell cycle, driving cell cycle progression? 1. a) Cyclin 8.33% ü 2. b) CDK (Cyclin-Dependent Kinase) 91.67% 3. c) p53 0% 4. d) DNA polymerase 0%  Join: vevox.app ID: 102-353-245POLL. What is the primary function of the G2 checkpoint in OPEN the cell cycle? ü 1. a) To check for DNA damage and repair it 32.76% 2. b) To ensure proper chromosome segregation 1.72% 3. c) To monitor DNA replication 8.62% 4. d) To decide whether to enter the M phase 56.9%  Join: vevox.app ID: 102-353-245POLL In cancer, what happens to the normal control OPEN mechanisms of the cell cycle? 1. a) They become more efficient. 0% 2. b) They are unaffected. 21.05% ü 3. c) They are lost or disrupted. 73.68% 4. d) They speed up without any issues 5.26%