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

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.

GENOME

• THE TOTAL HEREDITARY MAKE-UP OF A CELL OF A PARTICULAR SPECIES

• GENOMES ARE ORGANIZED INTO MULTIPLE FUNCTIONAL UNITES CALLED CHROMOSOMES

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

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

OVERVIEW VIDEO

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THE CELL CYCLE

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

M PHASE

• THE SHORTEST PART OF THE CELL CYCLE

• MITOSIS-DIVISION OF THE NUCLEUS

• CYTOKINESIS-DIVISION OF CYTOPLASM

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

THE CELL CYCLE

INTERPHASE

• G1= FIRST GROWTH

• S = SYNTHESIS PHASE OCCURS WHEN DNA IS MADE AS CHROMOSOMES ARE DUPLICATED

• G2 = SECOND GROWTH PHASE

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

LATE INTERPHASE VIDEO

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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

PROPHASE VIDEO

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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

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

PROMETAPHASE VIDEO

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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

METAPHASE VIDEO

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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

ANAPHASE VIDEO

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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

TELOPHASE VIDEO

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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

CYTOKINESIS VIDEO

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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

BINARY FISSION

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

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

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”

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)

CELL CYCLE CHECKPOINTS

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

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

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

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

MPF-CYCLIN ACTIVITY

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

DENSITY-DEPENDENT INHIBITION

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

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

METASTASIS