What is the cell cycle ?
-The cell cycle is the period of time between the birth of a cell and its own division to produce two daughter cells
-It lasts for at least 12 hours, but in the majority of adult tissues, it lasts much longer
Nerve cells stop dividing after baby is born but gial cells have tendency to deivide further
Liver and its cell can regeneratres from up to 2/3 removal
Where did the cell cycle concept arise from ?
The concept of cell cycle arose from study of different kind of cell growing invitro
When do some cells divide ?
Some cells in-vitro divide continuously at regular intervals
-Generally, it means that this cells undergo regularly a series of changes in structure and function and always ends with their return with the same structural and functional state that they were initially.
-Conclusion: At each mitosis two daughter cells are formed and after a definite interval each of this daughter cells will undergo another mitosis
-Cells that continue to divide regularly in definite intervals are described as cycling cells
What are the two basic parts of the cell cycle ?
1) The mitotic phase
2) Interphase (consists of G1, S, and G2 phase)
What is the role of cyclins in the cell cycle ?
-The cyclins are a family of proteins whose concentration increases and decreases throughout the cell cycle.
-Cell cycle protein molecules are cyclins A,B and E
-The cyclins activate and stimulate cyclin dependent kinases (CDKs - enzymes) which act in conjunction with cyclins (to help cell through cell cycle)
-Upon completion of cell cycle, cyclins and CDKs are degraded: the residues of used molecules are taken up by cytoplasmic care taker protien; ubiquitin
What is interphase
The interval between the end of mitosis and beginning of next
Cell is either resting or performing its specialised work not in mitosis
There are no divisions in interphase
What occurs during S phase ?
-Relation of DNA to genes is established
-DNA would have to be duplicated (replication) sometime in the cell cycle to have enough genes for two daughter cells
-DNA duplicate not in mitosis but during interphase long before the chromosomes are detected as thread like bodies
-So, the period in which new DNA is synthesized termed as S phase (S for synthesis) of cell cycle
-Begins 8 hours after the end of mitosis and take about 7 to 8 hours to complete
-The phase is promoted by cyclin A and CDKs
Read over page 10 and 11 of the powerpoint from week one FiM. Actually whats the drug called ?
Do it !! Drug is called dactinomycin (actinomycin D)
Describe important points about DNA replication
-DNA replication occurs in S phase
-DNA can be damaged during replication
-Repair mechanisms exist for DNA damage
-Defects in these repair mechanisms cause disease
What is G1 phase ?
-The gap in the cell cycle between the end of mitosis and beginning of S phase is termed as G1 Phase (G for gap)
-G1 shows considerable variation, sometimes ranging from less than 2 hours in rapidly dividing cells, to more than 100 hours within the same tissue
-G1 is the period when cells respond to growth factors directing the cell to initiate another cycle; once made, this decision is irreversible. It is also the phase in which most of the molecular machinery required to complete another cell cycle is generated.
-The phase is controlled by cyclin E and CDKs
Growth factors make cell undergo functional and structural changes
What is G0 phase ?
-Cells that retain the capacity for proliferation and in the process of differentiation, but which are no longer dividing, have entered a phase called G0 and are described as quiescent. They do not enter S phase
-Growth factors can stimulate quiescent cells to leave G0 and re-enter the cell cycle, whereas the proteins encoded by certain tumour suppressor genes (e.g. the gene mutated in retinoblastoma, Rb) block the cycle in G1
Once get stimulated out of G0 by growth factors the celll can then go into and enter G1, then S phase and so on
What is G2 phase ?
-The gap between the end of S phase and beginning of mitosis is the G2 phase
-Takes 2 to 4 hours to complete
-During G2, the cell prepares for division; this period ends with the breakdown of the nuclear membrane and the onset of chromosome condensation
-The phase is controlled by cyclin B and CDKs
Cyclib B and CDKs drives/stimuates cell in this stage towards mitosis
Once cell is in G2 the nucelar membrane dissapears and chromosmes condense so they look very chromosomey and nice and you can see them clearly
What are facts about interphase ?
-In interphase individual chromosome are not visible. They are uncoiled into very long narrow structures
-During interphase, the nucleus of the cell possess a nuclear envelope and contains a network of chromatin threads or granules and a nucleolus
-Replication of DNA takes place in chromosome
-Outside the nuclear envelope two paired centrioles are located in cytoplasm
Give a summary of mitosis ?
-Mitosis occurs in most somatic cells
-It results in the distribution of identical copies of the parent cell genome to the two daughter cells
The nuclear changes that achieve this distribution are conventionally divided into four
phases:
-Prophase
-Metaphase
-Anaphase
-Telophase
What occurs during prophase ?
-The individual chromosome are first visualized as thin threads and are tightly coiled along the entire length.
-Each chromosome splits longitudinally into two chromatids except at the centromere.
-The two paired centriole are separated from each other by elongation of continuous microtubules of the achromatic spindle and occupy the opposite pole of nucleus.
-The prophase take about 1.5 hours to complete
What occurs in prometaphase ?
-Subsequent (to prophase), the nuclear membrane and nucleolus disappear
-The chromosomes are now entangled in a meshwork of continuous microtubules
What occurs in metaphase ?
-Centromere region from each chromosome presents a bilateral disc Kinetochores
-From kinetochores, a set of chromosomal microtubules are organized and extend bilaterally towards opposite centrioles
-The growth of the chromosomal microtubules allows centromere of individual chromosomes with their paired chromatids to occupy equatorial plane of the spindle
-Metaphase persists for 20 minutes
What is colchicine ?
-Colchicine arrest the cell division at metaphase
-Colchicine prevents the formation of microtubules of the spindle (so chromosomes do not line up)
-In colchicine treated metaphase the chromosomes are found to assemble around centriole
-Application of colchicine in cell culture is a important tool in karyotyping
-This underpins the rationale for many types of cytotoxic drugs used in cancer therapy
Centrioles next to nucleus so chromosomes are next to them by default
What occurs during anaphase ?
-The centromeres split longitudinally and chromatids separate to form two new chromosome
-The spindle fibres contract, each pair of newly formed chromosomes separates and migrates to the opposite pole of the spindle. Two identical and complete chromosomes are formed.
-The separation of the chromatids to form new chromosomes occurs by contraction of chromosomal microtubules which exert a centrifugal force in centromere region.
What is non-disjunction ?
-Due to abnormal function of spindle apparatus one or more chromosomes fail to migrate properly in anaphase
-This leads to non-disjunction where one daughter cell receives extra chromosomes and other daughter cell is deficient in this chromosome
(Microtubules shuld have equal force, but when this happens the force of one is greater than the other so chromosomes arent pulled or split properly, so one cell gets extra chromosome and the other misses one)
What is an isochromosome ?
-Sometimes, the centromere splits transversely instead of longitudinal division.
-This leads to formation of two daughter chromosome of unequal length. This is known as Isochromosome
Most likely to occur in early anaphase
What is telophase ?
-It is a reorganization period
-The daughter chromosomes are enveloped by new nuclear membrane and nucleolus appears
-The chromosomes become uncoiled and their individual identity is lost.
-The cytoplasm divides and two complete cells are formed
What is cytokineses ?
-In the process of cytokinesis, the cleavage furrow develops around the equator region of achromatic spindle.
-The contraction of fibrillar component of cytoplasm help in hour glass constriction of cleavage