A presentation about cell cycle and the check mechanism. Pictures are copied from internet. all credit of the pictures goes to the original creator.
- 1. Cell CycleAbish Adhikari, ResidentDepartment of Radiation
Oncology NAMS, [email protected] 1
2. Introduction A cycle of events that a cell completes fromone
division to the next is called the cell cycle.-Perez & Bradys 2
3. 3Cell cycle Time Time (h r s) HeLa Cell Hamster CellTotal cell
cycle time24 11Mitosis1 1S- phase 8 6G2 4 3G1 111 3 4. 4 5. Cell
CycleInterphase: time between divisions G1, S, and G2Mitosis:
division of the chromosomesCytokinesis: division of the
cytoplasmCheckpoints in the cell cycle regulate celldivision6 6.
InterphaseG1 Begins immediately after division New organelles
formed End of G1, cell has doubled in sizeS phase Duplicate copy of
each chromosomeG2 phase Cell prepares to begin mitosis7 7. G2/M
checkpoint 4 Cell division3 DNArepairMitosis1G2 Cell grows, doubles
inG1 sizeS Chromosome2 duplication 8 G1/S checkpoint Stepped Art p.
181 8. Interphase 9 9. MitosisThe process by which cells
reproducethemselves, resulting in daughter cells thatcontain the
same amount of geneticmaterial as the parent cell. 10 10. Stages of
Mitosis11 11. Stages of Mitosis: ProphaseReplicated chromosomes
condense andbecome visible.46 chromosomes composed of two
sisterchromatids.Nuclear membrane breaks down.Spindle fibers
form.12 12. Prophase 13 13. Stages of Mitosis:
MetaphaseChromosomes, with spindle fibers attached,move to middle
of cell 14 14. Stages of Mitosis: AnaphaseCentromeres
divide.Converts each sister chromatid to achromosome.Chromosomes
migrate to opposite ends of cell.Complete set of 46 chromosomes at
each endof cell. 15 15. Anaphase 16 16. Stages of Mitosis:
TelophaseFinal stage of mitosisChromosomes unwindSpindle fibers
break downNuclear membrane re-forms 17 17. Cytokinesis: Last Stage
of Cell CycleCell membrane constricts and divides cell intotwo
daughter cells with 46 chromosomes 18 18. Identical Daughter Cells
19 19. Control of Cell Cycle Internal and external signals Either
stimulates or inhibits a metabolic event. 20 20. 21 21.
HuntHartwellNurse(2001 AD)This years Nobel Laureates have
discovered the key regulators of the cell cycle- cyclin dependent
kinase(CDK) and cyclin. Together these two components form an
enzyme, in which CDK is comparable to a molecularengine that drives
the cell through the cell cycle byaltering the structure and
function of other proteins in thecell. Cyclin is the main switch
that turns the CDK engine on and off. This cell-cycle engine
operates in the same way in such widely disparate organisms as
yeast cells, 22 plants, animals, and humans. 22. Cyclins / CDKs /
CKIs23 23. Cell-cycle checkpointsRestriction point Regulate
initiation ofDNA replicationG2-M checkpoint Checks DNAdamageSpindle
checkpoint Checks chromosomealignment24 24. DNA Damage Check Point
DNA Damage can be checked at varioussites. (Before S, During S,
After S ) Detected by DNA bound proteins ATM & ATR.
Transcription factor p53 is activated afterdamage is detected.
(guardian of genome) It activates p21 ( a CKI) that blocks CDK2/4.
25 25. Replication Checkpoint Before entering the M phase of the
cycle. If some errors in the replication of the genomeis identified
by chk1 and CDC25C. The activation of CDK1 is prevented thuscausing
prevention of M phase of cycle.26 26. Spindle Integrity
checkpointmicrotubules in green, chromosomes in blue, and
kinetochores in pink 27 27. Spindle Integrity Checkpoint The most
dangerous time for a cell. -Devita Aligning duplicated chromosomes
by attachingthem to bipolar attachments to the spindle. The sensors
of this check point are present inthe kinetochores. APC/C Cofactor
~ CDC20 is inhibited unlessthere is equal tension on both the
sides. CDC20 when active inhibits securin whichthen enables the
seperation process. 28 28. 29 29. Cell Cycle and Cancer Cancer is
partly a disease of uncontrolledproliferation. Cell cycle and check
point genes are foundmisregulated / mutated in cancer.
Protooncogenes Tumor Supressor Genes 30 30. Cancer Cells 31 31.
Protooncogene / Oncogene A proto-oncogene is a normal gene that
canbecome an oncogene due to mutations. The resultant protein :
oncoprotein. The mutations are generally dominant. Examples: SRC,
RAS, WNT, MYC, cSIS 32 Pancreas colon breast burkitts GBM 32. Tumor
Supressor Gene ~ anti-oncogene. Mutations in these genes cause loss
offunction, thus causing malignancy. Mutations are generally
recessive, thusheterozygosity is necessary for mutation to
beapparent. two-hit hypothesis Examples: pRb, p53, APC, BRCA 33 33.
34 34. Proto-Oncogene RASProduces RAS protein that: Attaches to
inside of plasma membrane Is part of a pathway that turns on cell
division Is signaled by growth factors from outside the cellRAS
mutations in many types of cancer,including colon, lung,
pancreatic, and stomachcancerMutant RAS stuck on and
produces35uncontrolled cell division. 35. BRCA1 Described in 1970s
after analyzing pedigrees of 1,500 families. In 1990, identified in
chromosome 17 Dominantly inherited, carry one mutant copy gene,
develop breast cancer if other copy mutates82%: breast cancer44%:
ovarian cancer 36Another gene BRCA2 is in Chromosome 13, rare and
causes susceptibility to breast cancer. 36. Thank You37
