Chromosomes structure and Cell cycle

1. Chromosomes structure and Cell cycle

2. Genetic Material in the Living Cells • In a non-dividing cell the nucleus is filled with a thread-like material known as "chromatin". • Chromatin is made up of DNA and proteins (mainly histones and some non-histone acidic proteins). • Chromosome is a combination of two words, i.e., “Chroma”-means ‘colour’ and “Somes”-means ‘body’.

3. Chromosomes are the nucleoprotein structures that carry the genetic information. In eukaryotes they are located in the cell nucleus.

4. Chromosomes • The eukaryotic genome is made up of DNA/protein complexes called chromosomes. • Gene sequences embedded within chromosomes must still be available for transcription by RNA polymerases and all of the DNA must be capable of being copied by DNA polymerases. • Chromosomes have two main functions: • To ensure that the DNA is segregated equally to daughter nuclei at cell division, and to ensure that the integrity of the genome is maintained and accurately replicated in each cell cycle. • The elements responsible for these functions are centromeres, telomeres and replication origins, respectively

5. Each chromosome carries a couple of thousand genes. • Many of these are common to all human beings. • So, 99.9%of your DNA is identical to everyone else's. • The remaining 0.1% influences the differences between us. • height, hair color and susceptibility to a particular disease. • Environmental factors, such as lifestyle also influence the way we look and our susceptibility to disease

6. Chromosome number/size • There are mainly two type: • Somatic chromosome number (2n), it is the number of chromosome found in somatic, merismatic and tissues of species. • Gametic chromosome (n), it is one half of the somatic number basically it is the haploid number. • Chromosome size shows variation depending upon stage of cell division, it is from 1 to 30 in length and diameter from 0.2 to 2 . • Longest and thinnest chromosome seen during interphase.

7. Chromosome morphology • Chromatid:Two chromatids join at the centromere to form a chromosome. • Centromere:are attachment points for the mitotic spindle. This attachment is essential for the equal and orderly distribution of chromosome sets to daughter cells, thus it is play a key role in stable chromosome segregation during cell division. Centromere is an A-T regions. • Telomere:specialized sequences at the ends of a chromosome that protect and stabilize the entire chromosome, by protecting the ends from nucleases and providing unique mechanisms for the faithful replication of linear DNA molecules. Contain short, repeat TG-rich element.

8. Types of chromosomes • There are four types of chromosomes based upon the position of the centromere. • Metacentric: the centromere occurs in the centre and all the four chromatids are of equal length. • 2) Submetacentric: the centromere is a little away from the centre and therefore chromatids of one side are slightly longer than the other side. • 3) Acrocentric: the centromere is located closer to one end of chromatid therefore the chromatids on opposite side are very long. • 4) Telocentric:the centromere is placed at one end of the chromatid and hence only one arm. Such telocentric chromosomes are not seen in human cells.

9. Comparison between Mitosis and Meiosis

10. Summary:

11. Chromosomes and cell division • Multicellular organisms copy their chromosomes before cell division. • They must grow to a mature size. • The nucleus divides, distributing the chromosomes into two equal groups (mitosis). • The cytoplasm then divides (cytokinesis) each part taking a nucleus. Interphase

12. Review Questions • What are and what happens during the phases of the cell cycle? • Which proteins are involved in the regulation of the cell cycle? • Which cyclins and cyclin-dependent kinases are most important in individual phases of the cell cycle? • What are four mechanisms for regulating cyclin-dependent kinase activity? • What role do p53, p21, and pRb play in the G1 to S transition?

13. The cell cycle

14. The Cell Cycle • Cells must accomplish two basic things during the cell cycle: • Copying cellular components • 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”. • The “division” activity corresponds to “M phase”. • The “growth” activity corresponds to “Interphase”.

15. Continue.. • The timing and rates of cell division in different parts of an animal or plant are crucialfor normal growth, development, and maintenance. • The frequency of cell division varies with cell type. • Some human cells divide frequently throughout life (skin cells), others have the ability to divide, but keep it in reserve (liver cells), and mature nerve and muscle cells do not appear to divide at all after maturity.

16. A molecular control system drives the cell cycle • The cell cycle appears to be driven by specific chemical signals in the cytoplasm. • Fusion of an S phase cell and a G1 phase cell induces the G1 nucleus to start S phase. • Fusion of a cell in mitosis with one in interphase induces the second cell to enter mitosis.

17. Continue... • The distinct events of the cell cycle are directed by a distinct cell cycle control system. • These molecules trigger and coordinate key events in the cell cycle. • The control cycle has a built-in clock, but it is also regulated by external adjustments and internal controls. • A checkpoint in the cell cycle is a critical control point where stop and go signals regulate the cycle. • Three major checkpoints are found in the G1, G2, and M phases.

18. You must know that the order of the cell cycle is:   Interphase, Prophase, Metaphase, Anaphase, Telophase, Cytokensis (IPMATC). • From Prophase to Telophase is what is known as Mitosis.

19. Continue... • For many cells, the G1 checkpoint, the restriction point in mammalian cells, is the most important. • If the cell receives a go-ahead signal, it usually completes the cell cycle and divides. • If it does not receive a go-ahead signal, the cell exits the cycle and switches to a nondividing state, the G0 phase. Most human cells are in this phase.

20. Control of the Cell Cycle • The abundance and activity of control molecules pace the cell cycle. • Some molecules are protein kinases that activate or deactivate other proteins by phosphorylating them. • The levels of these kinases are present in constant amounts, but these kinases require a second protein, a cyclin, to become activated. • Levels of cyclin proteins fluctuate cyclically. • The complex of kinases and cyclin forms cyclin-dependent kinases (Cdks). • Cyclin levels rise sharply throughout interphase, then fall abruptly during mitosis.

21. Cyclins • Four classes Defined by phase of the cell cycle in which they bind their cdk: • G1/S phase cyclins- bindcdks at the end of G1, commit cell to DNA replication (cyclin E). • S phase cyclins-bind cdks during S phase, required to initiate replication (cyclin A). • M phase cyclins- bindcdks immediately before M phase, initiate early mitotic (or meiotic) events (cyclin B). • G1 cyclins- involved in progression through the checkpoint in late G1 (cyclin D).

22. M phase Promoting Factor (MPF) • MPF “maturation-promoting factor” or “M-phase-promoting-factor” triggers the cell’s passage past the G2 checkpoint to the M phase. • MPF promotes mitosis by phosphorylatinga variety of other protein kinases. • Stimulates fragmentation of the nuclear envelope. • It also triggers the breakdown of cyclin, MPF only active when cyclin levels high enough – triggers passage through G2 checkpoint. • The M phase checkpoint ensures that all the chromosomes are properly attached to the spindle at the metaphase plate before anaphase. • This ensures that daughter cells do not end up with missing or extra chromosomes.

23. Rb protein

24. p53: Tumor SuppressorGene

25. Cells Which No Longer Respond to Cell-Cycle Controls • Cancer cells do not respond normally to the body's control mechanism. • They divide excessively and invade other tissues • If left unchecked, they can kill the organism • Cancer cells do not exhibit contact inhibition • If cultured, they continue to grow on top of each other when the total area of the petri dish has been covered. • They may produce required external growth factor themselves or possess abnormal signal transduction sequences which falsely convey growth signals thereby bypassing normal growth checks • Cancer cells exhibit irregular growth sequences • If growth of cancer cells does cease, it does so at random points of the cell cycle • Cancer cells can go on dividing indefinitely if they are given a continual supply of nutrients