Ch. 12 Cell cycle

Oct 1 ­ 4:01 PM 1 Key roles of cell division (reproduction) 1. one cell can produce a whole organism ex. Amoeba

2. can produce progeny from multicellular organisms ex. plants from cuttings

Oct 1 ­ 4:02 PM 2 3. sexually reproducing organisms can develop from a single cell ex fertilized egg

4. renewal and repair of mature cells ex bone marrow makes new blood cells

Oct 16­9:11 AM 3 Cell division is part of cell cycle

Cell cycle= the life of a cell from first formation from parent cell until its own division into two cells

­generally results in two daughter cells identical (a clone) to parent cell by copying and distributing identical DNA to each cell

Oct 1 ­ 4:07 PM 4 Genome = All of a cell's DNA ­prokaryote ­Long single piece of DNA­ circular ­eukaryote ­ many DNA molecules ­human = 2­3 m of DNA

­DNA gets packaged into chromosomes ­each eukaryote has its own unique number of chromosomes in nucleus

Oct 1 ­ 4:10 PM 5 ­human somatic cells (all body cells except reproductive cells) have 46 chromosomes (23 pairs)

­gametes (sperm and egg cells) have 23 chromosomes

http://www.advancedfertility.com/sperm1.htm

Oct 16­9:14 AM 6 Chromatin = a complex of DNA and proteins = uncoiled chromosomes ­when cell is not dividing, DNA is in long fibers of chromatin ­DNA replicates ­When dividing, cell coils up the chromatin into chromosomes

­each duplicated chromosome has two sister chromatids connected by a centromere

Oct 1 ­ 4:17 PM 7 Sister chromatids eventually separate and move into two new nuclei during cell division

Oct 1 ­ 4:21 PM 8 Mitosis = division of the nucleus

Cytokinesis = division of the cytoplasm

Meiosis = cell division that produces gametes ­occurs only in gonads (ovaries/testes) ­reduces # of chromosomes from 46 to 23

Oct 1 ­ 4:22 PM 9 Walther Flemming was the first scientist to study the cell cycle ­ 1882 used dyes to see the cell components

Oct 1 ­ 4:25 PM 10 Phases of the Cell Cycle

I. Interphase ­90% of cycle G1 phase ("1st gap") = cell grows in size and components ( makes proteins, cytoplasmic organelles ­ all three phases), 5­6 hrs

Oct 1 ­ 4:26 PM 11 S phase ("synthesis") = chromosomes are duplicated, 10­12 hours

G2 phase ("second gap") = two centrosomes have formed from one centrosome, cell still grows, 4­6 hrs.

Jan 26­12:12 PM 12 II. Mitotic phase ­ 1 hr. =division of nucleus

a. Prophase ­chromatin fibers become coiled into chromosomes ­nucleoli disappear ­can see sister chromatids ­mitotic spindle begins to form ­centrosomes move away from each other, due to lengthening microtubules

Oct 1 ­ 4:34 PM 13 Oct 16­9:30 AM 14 b. Prometaphase ­nuclear envelope starts to break up ­microtubules of spindle fibers can now attach to chromosomes ­chromosomes become more condensed ­microtubules extend from centrosome to middle of cell ­kinetochore attaches to each chromatid of sister chromatids

Oct 1 ­ 4:38 PM 15 ­kinetochore = specialized protein structure located in centromere

­kinetochore microtubules jerk chromosomes back and forth ­nonkinetochore microtubule interact with opposite pole

Jan 26­12:15 PM 16 c. Metaphase ­longest stage of mitosis ­ 20 minutes ­centrosomes at opposite poles at metaphase plate (imaginary plane equidistant between two poles) ­chromosomes line up on metaphase plate with centromeres in the middle ­kinetochores of sister chromatids are connected to kinetochore microtubules of opposite poles ­spindle = all microtubules at this point

Oct 1 ­ 4:44 PM 17 d. Anaphase ­shortest stage of mitosis ­ few minutes ­two sister chromatids come apart ­ becomes chromosome ­chromosomes move towards opposite poles, pulled by kinetochore microtubules that shorten ­cell elongates ­ nonkinetochore microtubules lengthen ­at end of anaphase each side of the cell has complete set of chromosomes

Oct 1 ­ 4:49 PM 18 e. telophase ­two daughter nuclei begin to form ­nuclear envelopes arise from fragments of nuclear envelope of parent ­chromosomes are less condensed ­mitosis is complete

Oct 1 ­ 5:14 PM 19 Oct 16­9:31 AM 20 III. Cytokinesis ­division of cytoplasm ­animals ­ cleavage furrow, cell pinches together at site of old metaphase plate (is a ring of actin microfilaments with myosin­ like drawstrings) ­plants­ no cleavage furrow ­Golgi apparatus vesicles move along microtubules to middle of cell to make a cell plate ­cell plate gets bigger and fuses with plasma membrane and a new cell wall appears

Oct 1 ­ 5:16 PM 21 Oct 16­9:34 AM 22 Mitotic Spindle ­made of fibers of microtubules and proteins diassembled from cytoskeleton elsewhere in cell

Oct 1 ­ 5:23 PM 23 elongate by adding more tubulin units ­assembly starts at centrosome (organizes cell microtubules) ­animal cells have centrioles in center of centrosomes ­plant cells lack centrioles, but still have centrosomes ­during prometaphase spindle microtubules attach to kinetochores (help chromosome move to poles)

Oct 16­9:32 AM 24 nonkinetochore microtubules­ responsible for elongation of whole cell during anaphase ­overlap each other on the metaphase plate ­not attached to kinetochores

Oct 1 ­ 5:29 PM 25 Mitosis in a plant cell

Oct 16­9:34 AM 26 Onion Root Tip

Oct 16­9:35 AM 27 Other cell division ­ Binary Fission ­in prokaryotes ­DNA of bacteria replicates at the origin of replication (makes two origins) ­one origin moves towards the other side of cell ­cell elongates to be twice normal size ­plasma membrane grows inward dividing into two cells ­ each with complete genome

Oct 1 ­ 5:33 PM 28 bacteria do not have microtubules or mitotic spindles ­proteins may play a role in helping DNA get to each side

Jan 26­12:21 PM 29 Binary Fission

Oct 16­9:36 AM 30 Evolution of Mitosis

Oct 1 ­ 5:38 PM 31 Cell Cycle is regulated by signals

1970 experiment Evidence for cytoplasmic chemical signals in cell cycle regulation

Oct 16­9:37 AM 32 Cell cycle control system

­are molecules that trigger the events of cell cycle ­checkpoints = critical control point where stop and go ahead signals regulate the cycle ­can be regulated by inside or outside cell ­major ones are found in G1, G2 and M phases

Oct 1 ­ 5:40 PM 33 Oct 16­9:46 AM 34 G1 checkpoint = restriction point in mammals ­if cell receives go ahead at this point cell will complete S, G2 and M phases and divide ­if no "go" then will exit cycle and go to Go phase ­most cells are in Go phase ­cells can go from Go phase back into cell cycle

Oct 1 ­ 5:45 PM 35 regulatory molecules control the cycle = kinases [protein kinases ­ ( by phosphorylation)] and cyclins ­protein kinases give go ahead at G1 and G2 checkpoints ­kinase attaches to cyclin to become active = cyclin dependent kinases ­ Cdks Cdk complex = MPF (maturation­promoting factor) ­Cdk concentration goes up and down depending on concentration of cyclin

Oct 1 ­ 5:49 PM 36 **When cyclin accumulates during G2 with Cdk molecules, MPF complex initiates mitosis, by phosphorylating proteins

MPF promotes fragmentation of nuclear envelope during prometaphase ­also may be involved in chromosomes condensation and spindle formation

Oct 1 ­ 5:55 PM 37 Molecular control of cell cycle at G2 checkpoint

Oct 16­9:49 AM 38 Internal and external signals at checkpoints

1. essential nutrients needed 2. growth factor ­ protein that promotes cell division (called a mitogen) ex. platelet­derived growth factor (PDGF) ­made by platelets ­ needed for division of fibroblasts (connective tissue cell)

Oct 1 ­ 5:59 PM 39 ­PDGF is a signal molecule that binds to a receptor to imitate a signal transduction pathway ­ allows cell to pass G1 phase ­used in animal in healing wound process

Jan 26­12:27 PM 40 The Effect of Growth Factor on Cell division

Oct 16­9:51 AM 41 3. Density­dependent inhibition ­used to stop crowded cells from dividing ­when a cell population gets to a certain size, nutrients become insufficient to allow more growth and division

Oct 1 ­ 6:05 PM 42 4. Anchorage dependence ­to divide must be attached to a substratum ­anchorage is signaled via pathways involving plasma membrane proteins and cytoskeleton elements

Oct 16­11:32 AM 43 Cancer = loss of cell cycle control because normal signals do not affect the cells ­don't exhibit density dependent inhibition ­cancer cells can divide at any point in the cycle not just at the checkpoints ex. HeLa cells 1951 original tumor from Henrietta Lacks cells from that tumor are still dividing in a lab ­normal cells divide 20­50 times and stop

Oct 1 ­ 6:09 PM 44 transformation = process that converts a normal cell to a cancer cell ­can form a tumor if gets past immune system ­ benign = abnormal cells in original state ­not problematic, removed surgically ­malignant = invasive so it affects the function of one or more organs = "cancer" ­cells also may have unusual # of chromosomes, metabolism problems, loss of attachments to adjacent cells ­Metastasis ­if some of tumor separates from original tumor and travels to rest of the body

Oct 1 ­ 6:15 PM 45 Metastasis of breast tumor

Oct 16­11:34 AM 46 Normal tumor

Oct 16­11:36 AM 47 Treatments for tumors

Radiation ­damages DNA in cancer cells ­used more for localized tumors

Chemotherapy ­ for metastasized tumors ­toxic drugs to cells are injected ­interfere with steps of cell cycle

Oct 1 ­ 6:23 PM 48 ex Chemotherapy treatment = Taxol ­freezes mitotic spindle by preventing microtubule formation, cells stop at metaphase ­has side effects due to interaction with normal cells (nausea, hair loss, susceptibility to infection)

Jan 26­12:31 PM 49 Oct 16­11:37 AM 50