CHAPTER 12

1. CHAPTER 12 MITOSIS THE CELL CYCLE

2. MITOSIS-CELL DIVISION • THIS IS A FINELY CONTROLLED PROCESS THAT RESULTS IN TWO IDENTICAL DAUGHTER CELLS. A DIVIDING CELL: • PRECISELY REPLICATES ITS DNA • ALLOCATES THE TWO COPIES OF DNA TO OPPOSITE ENDS OF THE CELL • SEPARATES INTO TWO DAUGHTER CELLS CONTAINING IDENTICAL DNA

3. SOMATIC CELLS • MITOSIS IS THE PROCESS BY WHICH ALL CELLS IN THE BODY (SOMATIC CELLS) ARE MADE, EXCEPT FOR SEX CELLS (GAMETES). THESE ARE MADE THROUGH MEIOSIS, WHICH WE WILL COVER IN THE NEXT CHAPTER.

4. GENOME • THE TOTAL HEREDITARY MAKE-UP OF A CELL OF A PARTICULAR SPECIES • GENOMES ARE ORGANIZED INTO MULTIPLE FUNCTIONAL UNITES CALLED CHROMOSOMES

5. CHROMOSOMES • EACH CHROMOSOME CONSISTS OF TWO SISTER CHROMATIDS. THE TWO CHROMATIDS HAVE IDENTICAL COPIES OF THE CHROMOSOME’S DNA AND INITIALLY ATTACHED TO EACH OTHER AT THE CENTROMERE

6. MITOSIS OVERVIEW • 1) IN PREPARATION FOR DIVISION, CHROMOSOMES AND ALL CELL PARTS ARE DUPLICATED • 2) DURING MITOSIS, SISTER CHROMATIDS ARE PULLED APART, ONE SET AT EACH END OF THE CELL • 3) CYTOKINESIS IS THE DIVISION OF THE CYTOPLASM INTO TWO SEPARATE DAUGHTER CELLS

7. OVERVIEW VIDEO

8. THE CELL CYCLE • THE CELL CYCLE ALTERNATES BETWEEN THE MITOTIC (M) PHASE, OR DIVIDING PHASE, AND INTERPHASE, THE NONDIVIDING PHASE.

9. M PHASE • THE SHORTEST PART OF THE CELL CYCLE • MITOSIS-DIVISION OF THE NUCLEUS • CYTOKINESIS-DIVISION OF CYTOPLASM

10. INTERPHASE • THE NONDIVIDING PHASE, INCLUDES MOST OF A CELL’S GROWTH AND METABOLIC ACTIVITIES • ABOUT 90% OF CELL CYCLE • INTENSE BIOCHEMICAL ACTIVITY; COPYING OF CHROMOSOMES AND ALL ORGANELLES • CONSISTS OF THREE PERIODS: G1, S, G2

11. THE CELL CYCLE

12. INTERPHASE • G1= FIRST GROWTH • S = SYNTHESIS PHASE OCCURS WHEN DNA IS MADE AS CHROMOSOMES ARE DUPLICATED • G2 = SECOND GROWTH PHASE

13. G2 PHASELATE INTERPHASE • A G2 CELL SHOWS: • A WELL DEFINED NUCLEUS WITH NUCLEAR ENVELOPE • ONE OR MORE NUCLEOLI • TWO CENTROSOMES • A PAIR OF CENTRIOLES IN EACH CENTROSOME (ANIMAL CELLS ONLY) • ASTERS AROUND CENTRIOLES • DUPLICATED CHROMOSOMES ARE LOOSELY PACKED CHROMATIN FIBERS

14. LATE INTERPHASE VIDEO

15. PROPHASE • IN THE NUCLEUS • NUCLEOLI DISAPPEAR • CHROMATIN FIBERS CONDENSE IN THE CYTOPLASM -MITOTIC SPINDLE FORMS; IT IS MADE OF MICROTUBULES -CENTROSOMES MOVE APART, MOVED ALONG THE NUCLEAR SURFACE BY LENGTHENING OF THE MICROTUBULE BUNDLES

16. PROPHASE VIDEO

17. PROMETAPHASE • NUCLEAR ENVELOPE FRAGMENTS; THIS ALLOWS MICROTUBULES TO INTERACT WITH CHROMOSOMES • SPINDLE FIBERS EXTEND FROM EACH POLE TOWARDS THE MIDDLE • EACH CHROMATID NOW HAS A SPECIALIZED STRUCTURE, THE KINTECHORE, LOCATED AT THE CENTROMERE REGION

18. PROMETAPHASE • KINETOCHORE MICROTUBULES BECOME ATTACHED TO KINETOCHORES AND PUT THE CHROMOSOMES INTO MOTION • OTHER MICROTUBULES RADIATE FROM EACH CENTROSOME TOWARD THE METAPHASE PLATE; THEY DO NOT ATTACH TO CHROMOSOMES

19. PROMETAPHASE VIDEO

20. METAPHASE • CENTROSOMES ARE AT OPPOSITE POLES OF THE CELL • CHROMOSOMES MOVE TO THE METAPHASE PLATE, MIDDLE OF SPINDLE POLES • CENTROMERES ARE ALIGNED ON THE METAPHASE PLATE • KINETOCHORES OF SISTER CHROMATIDS FACE OPPOSITE POLES, SO IDENTICAL CHROMATIDS ARE ATTACHED TO FIBERS FROM OPPOSITE ENDS OF PARENT CELL

21. METAPHASE VIDEO

22. ANAPHASE • SISTER CHROMATIDS SPLIT APART INTO SEPARATE CHROMOSOMES AND MOVE TO OPPOSITE POLES • CHROMOSOMES MOVE CENTROMERE FIRST IN A “V” SHAPE DUE TO KINETOCHORE FIBER ATTACHMENT TO CENTROMERES • KINETOCHORE MICROTUBULES SHORTEN • THE POLES OF THE CELL MOVE FARTHER APART, ELONGATING THE CELL

23. ANAPHASE VIDEO

24. TELOPHASE • NONKINETOCHORE MICROTUBULES FURTHER ELONGATE THE CELL • DAUGHTER NUCLEI BEGIN TO FORM • NUCLEAR ENVELOPES FORM AROUND THE CHROMOSOMES (FROM FRAGMENTS OF THE PARENT CELL’S NUCLEAR ENVELOPE) • NUCLEOLI REAPPEAR • CHROMATIN FIBER OF EACH CHROMOSOME UNCOILS AND CHROMOSOMES BECOME LESS DISTINCT

25. TELOPHASE VIDEO

26. CYTOKINESIS • MITOSIS, THE EQUAL DIVISION OF ONE NUCLEUS INTO TWO GENETICALLY IDENTICAL NUCLEI IS COMPLETE • CYTOKINESIS, THE PINCHING OF THE CYTOPLASM FORMING A CLEAVAGE FURROW, AND FINALLY THE APPEARANCE OF TWO SEPARATE CELLS • PLANT CELLS: FORM A CELL PLATE BETWEEN CELLS

27. CYTOKINESIS VIDEO

28. BACTERIABINARY FISSION • PROKAROTES REPRODUCE BY BINARY FISSION, WHICH MAY BE THE EVOLUTIONARY PRECURSOR TO MITOSIS • THE CHROMOSOME IS REPLICATED AND REMAINS ATTACHED TO MEMBRANE • BETWEEN ATTACHMENT SITES, THE MEMBRANE GROS AND SEPARATES THE TWO COPIES OF CHROMOSOMES • THE BACTERIA GROWS TO TWICE ITS SIZE AND MEMBRANE PINCHES INWARD • A CELL WALL FORMS ACROSS THE BACTERIUM BETWEEN THE TWO CHROMOSOMES

29. BINARY FISSION

30. REGULATION OF THE CELL CYCLE • NORMAL GROWTH, DEVLOPMENT AND MAINTENANCE DEPEND ON THE TIMING AND RATE OF MITOSIS. CELL TYPES DIFFER IN THEIR PATTERNS OF DIVISION: • HUMAN SKIN CELLS DIVIDE OFTEN • LIVER CELLS ONLY DIVIDE WHEN NEEDED, AS IN WOUND REPAIR • NERVE AND MUSCLE CELLS TO NOT DIVIDE IN MATURE HUMANS

31. THE CELL CYCLE CONTROL SYSTEM • THIS IS A MOLECULAR CLOCK AND A SET OF CHECKPOINTS, THAT ENSURE THAT CONDITIONS ARE MET BEFORE CYCLE ADVANCES. MALFUNCTIONS IN SYSTEM CAN RESULT IN CANCER

32. THE CHECKPOINTS(G1, G2, AND M PHASES) • SIGNALS AT CHECKPOINTS REPORT STATUS OF CELL CONDITIONS (e.g., FAVORABLE ENVIRONMENT?, CELL BIG ENOUGH?, DNA COPIED?) • CHECKPOINTS INTEGRATE INTRACELLULAR AND EXTRACELLULAR INFORMATION • G1 CHECKPOINT MOST IMPORTANT: KNOWN AS THE “RESTRICTION POINT”

33. G1 CHECKPOINT • A GO-AHEAD SIGNAL INDICATES THAT CELL WILL COMPLETE CYCLE • IN ABSENCE OF GO-AHEAD, THE CELL MAY EXIT THE CELL CYCLE, SWITCHING TO NONDIVIDING STATE CALLED THE G0 PHASE • MANY CELLS OF HUMAN BODY ARE IN G0, (MUSCLE, NERVE, AND LIVER)

34. CELL CYCLE CHECKPOINTS

35. CELL CYCLE CONTROLLED BY PROTEIN KINASES • PROTEIN KINASES ARE ENZYMES THAT CATALYZE THE TRANSFER OF A PHOSPHATE FROM ATP TO TARGET PROTEIN • PHOSPHORYLATION INDUCES A CONFORMATIONAL CHANGE THAT EITHER ACTIVATES OR INACTIVATES A TARGET PROTEIN • CHANGES IN TARGET PROTEIN AFFECT THE PROGESSION THROUGH CELL CYCLE

36. CYCLINS: CONTROL KINASE ACTIVITY • THESE REGULATORY PROTEINS ARE NAMED CYCLINS, BECAUSE THEIR CONCENTRATIONS CHANGE THROUGHOUT THE CELL CYCLE • PROTEIN KINASES THAT REGULATE CELL CYCLE ARE CYCLIN-DEPENDENT KINASES (Cdks), AND ARE ONLY ACTIVE WHEN ATTACHED TO A CYCLIN

37. MPF: A CYCLIN-CDK COMPLEX • MPF: MATURATION PROMOTING FACTOR • CYCLIN’S CHANGES IN CONCENTRATION REGULATES MPF ACTIVITY, WHICH ACTS AS A MITOTIC CLOCK THAT REGULATES CHANGES IN THE DIVIDING CELL

38. MPF: THE PROCESS • CYCLIN IS PRODUCED AT A UNIFORM RATE THROUGHOUT CELL CYCLE, AND ACCUMULATE DURING INTERPHASE • CYCLIN COMBINES WITH CDK TO FORM ACTIVE MPF, WHICH REGULATES MPF CONCENTRATIONS • MPF PHOSPHORYLATES PROTEINS THAT PARTICIPATE IN MITOSIS AND INITIATES: • CHROMOSOME CONDENSATION DURING PROPHASE • NUCLEAR ENVELOPE FRAGMENTATION DURING PROMETAPHSE

39. MPF-CYCLIN ACTIVITY

40. FACTORS AFFECTING CELL DIVISION • CHEMICAL: GROWTH FACTORS NEEDED FOR CELL DIVISION • PHYSICAL: CROWDING INHIBITS CELL DIVISION; ALSO, MOST ANIMAL CELLS MUST ADHERE TO A SURFACE, WITHOUT WHICH CELL CYCLE IS SIGNALED TO STOP

41. DENSITY-DEPENDENT INHIBITION

42. CANCER CELLS • CANCER CELLS DO NOT STOP GROWING IN RESPONSE TO CELL DENSITY • CANCER CELLS MAY MAKE GROWTH FACTORS THEMSELVES • THEY MAY HAVE AN ABNORMAL GROWTH FACTOR SIGNALING SYSTEM • THEY CONTINUE TO DIVIDE INDEFINITELY, AS LONG AS NUTRIENTS ARE AVAILABLE

43. CANCER • TUMOR = AN UNREGULATED GROWING MASS OF CELLS • MALIGNANCY- TUMOR THAT IS INVASIVE ENOUGH TO IMPAIR NORMAL FUNCTION OF ONE OR MORE ORGANS • METASTASIS - MIGRATING CANCER CELLS INVADE OTHER PARTS OF BODY AWAY FROM ORIGINAL SITE

44. METASTASIS