1. Biology 205 Lecture 06: Mitosis and the cell cycle (and some meiosis review) Readings DO NOT POST THESE LECTURES!!! INSTRUCTOR VERSIONS

2. Text Readings Chapter 12: ALL Chapter 13: pp. 271 -282

3. Universal functions of the cell cycle Replicate the DNA. Replicate the DNA. Segregate it into daughter cells. Segregate it into daughter cells. Replicate and/or distribute organelles into daughter cells. Grow. M Phase = Mitosis + Cytokinesis

4. Universal functions of the cell cycle Mitotic or meiotic? Why?

5. FACS analysis (fluorescence-activated cell sorting) G1 G2

6. The logic of cell cycle control: Checkpoints Brakes Feedback Signals Inhibition of an activating phosphatase (Cdc25) blocks entry into mitosis Inhibition of an activating kinase (APC) delays exit from mitosis Cdk inhibitor (p27) blocks entry into S phase

7. What controls the cell cycle?

8. Molecular switches: cyclins & cyclin-dependent kinases

9. Activities Regulated by cyclin dependant kinases Are we ready for DNA replication? DNA replicated properly? Ready for the massive contortions of cell division? Are we ready to make a spindle? Are the chromosomes properly hooked up? Can we split chromosomes into chromatids? G1 G2 M

10. Different Cyclin-Cdk complexes control entry into each phase of the cell cycle P P Inhibitory phosphate group

11. Nobel Alert (2001)

12. DOWNSTREAM CONTROL What do Cdk’s regulate? M-phase cyclin dependent kinase phosphorylates condensin subunits to start chromosome condensation Chromosomes indistinct because decondensed Heterochromatin: more tightly packed chromatin Euchromatin: less tightly packed chromatin (most of the genes are here)

13. Cell shape changes prior to mitosis: what elements of cytoskeleton are involved?

14. FYI slide

15. Chromosomes Chromosomes Chromosomes are (usually) LONG pieces of double stranded DNA Can be linear (eukaryotic) or circular (prokaryotic) chromatin Can be complexed with proteins (chromatin) or almost naked nucleic acid Chromosome number can vary widely diploid Cells (and organisms) with two pairs of every chromosome in a set are diploid haploid Cells (and organisms) with only one of each chromosome in a set are haploid

16. Genomes

17. chromosomes, genomes and genes chromosomes The genome is the total information content represented by a single set of chromosomes Genome organization = the way in which this information is broken up and distributed over the chromosomes genes Information includes genes which are sequences of DNA located at specific positions along the chromosomes

18. Chromosomes and chromatids After the chromosomes replicate during S phase, two sister chromatids are joined together by the centromere When sister chromatids separate during mitosis, they can still be called chromatids but more accurately they are daughter chromosomes centromere S phase Non sister chromatids

19. haploid, diploid, polyploid Chromosome number: haploid, diploid, polyploid genome Talking about the number of chromosome sets that represent the genome information content of an organism The haploid set of chromosomes in an organism is a certain number = n (= ONE GENOME) In diploid organisms, where the chromosomes come in pairs, the total number of chromosomes is 2n Some organisms (some plants, some fish etc) are polyploid – they have multiple sets of chromosomes

20. Homologous chromosomes genes Members of a chromosome pair that contain the same genes homolog Each member is called a homolog One is inherited from each parent (so they are not identical) Chromosomes that contain different genes are non-homologous

21. M-Cdk drives entry into Mitosis telomeres

22. The enigmatic kinetochore inter

23. M-Cdk drives entry into Mitosis

24. The enigmatic kinetochore inter FYI slide

25. Cytokinesis

26. Contractile ring in animal cytokinesis Remember this?

27. Bacterial chromosome Human chromosome NOT to scale!!! replicated chromosome (can you see why?) What about prokaryotes?

29. Humans are diploid two of each chromosome –homologous pairs Members of a chromosome pair that contain the same genes Each member is called a homolog One is inherited from each parent (so they are not identical) Chromosomes that contain different genes are non- homologous

30. Humans are diploid two of each chromosome –homologous pairs Homologous pair of chromosomes

31. Humans are diploid two of each chromosome –homologous pairs Non-homologous pair of chromosomes

32. Autosomes and sex chromosomes In many eukaryotes, the sexes differ with respect to a single chromosome pair – these are the sex chromosomes In one sex they match (are homologous), and in the other they do not All the other chromosome pairs are autosomes

33. Human males are diploid, with unmatched sex chromosomes (XY)

34. Germ line versus somatic cells

35. Comparison of mitosis and meiosis http://www.pbs.org/wgbh/nova/baby/divi_flash.html

36. Homologous chromosome pairs undergoing crossing over at the sites of chiasmata. These pairs are also called “bivalents” or “tetrads” Stages of Meiosis I

37. Mixing genomes: crossing over

39. Metaphase, Anaphase and Telophase of Meiosis I How many chromosomes? How many genomes? What is the DNA content?

40. Mixing genomes: independent assortment Need figure 13-10 from new edition

41. Meiosis II

43. So why are YOU so different from mom and dad??? Two meiotic reasons Crossing over at Prophase I Independent assortment of chromosomes at anaphase I recombination BOTH are forms of recombination

44. Crossing over and independent assortment are happening in the same meiosis… Crossing over happens because homologs pair in meiosis I Independent assortment happens because the chromosomes segregate randomly at anaphase I after their random alignment at metaphase I

45. …and when you put them together in, say, a human context? 23 pairs of chromosomes, aligning on the metaphase plate independently of each other and segregating during the subsequent anaphase…well there’s a formula:  2 n where n = # chromosome pairs Plug in the numbers and you get…well…millions of possible combinations Add in recombination and, well….is it any wonder you’re different from mom and dad? What’s another ENORMOUS consequence of this variability?

47. Learning Objectives (Lecture 06)

48. UPSTREAM CONTROL: How are the Cdk’s regulated? (What regulates the regulators?)

49. Cell cycle regulation and Cancer