Chapter 9

I. Prokaryote Cell Division (Bacteria/Archaea) A. No nucleus so no mitosis B. No microtubules or motor proteins to move chromosome. C. Divide by Prokaryotic fission 1. single circular chromosome binds to cell membrane 2. DNA replication in both directions around circle 3. Cell divides by adding to cell membrane

II. Eukaryotic Cell Division A. DNA contained in nuclear membrane B. DNA replicated prior to cell division ( in interphase) C. Cell division divided into two parts 1. mitosis = division of nucleus 2. cytokinesis = division of cytoplasm D. Microtubules and microfilaments needed E. Motor proteins and ATP required

I. Mitosis A. produces clones (daughter cells) B. unicellular organisms : reproduction C. Multicellular organisms : 1. asexual reproduction (budding) 2. growth 3. replacement 4. repair

II. Meiosis A. produces haploid cells 1. chromosome number cut in ½ 2. non-identical cells 3. gametes B. only done for sexual reproduction

Somatic cell – normal diploid body cell Diploid cell – has 2 copies of each chromosome Haploid cell – has 1 copy of each chromosome Chromosome – naturally occurring segment of DNA and associated proteins

I. Chromatin - A. DNA wrapped around histones B. no supercoiling C. Most DNA available for transcription D. not visible under microscope II. Chromatid A. nucleosomes supercoiled into compact ‘arms’ B. DNA packaged for transport not use C. condensed chromosomes visible

Constriction in center = centromere = a region of DNA that binds to cohesin proteins that function to hold sister chromatids together Other cohesins hold sister chromatids together more loosely along their lengths

Identical Formed by semi-conservative replication While joined at centromere = 1 chromosome

unduplicated One chromosome One chromatid One double helix One chromosome (one centromere) Two chromatids Two double helixes duplicated

Genome = all of a cells DNA All eukaryotes have set # Chromosome in their genome Humans have 46 Two of each type… 23 different types

1) Tubulin subunits in centrosome begin to assemble into microtubules. 2) microtubules grow toward the center to form spindle fibers 3) short microtubules form a radial array called an aster 4) centrioles present in animals but not needed

Proteins located at centromere Attachment site for some microtubules of spindle Polar microtubules overlap with microtubules from opposite pole at center of cell

Polar microtubules

Centrosomes begin producing microtubules & moving toward opposite poles Nucleoli disappear. Chromosomes condense into… chromatids (pro-metaphase) Nuclear envelope breaks down Microtubules attach to … kinetochores Polar microtubules overlap at equator

Chromosomes lined up at equator Pulled by kinetochore microtubules C line up single file, One sister chromatid on each side Centrosomes reach poles

Cohesin proteins cleaved by Separase enzymes Separated sister chromatids move toward opposite poles Kinetochore microtubules shrink as they depolymerize at centrosome Motor proteins drag chromatids along shrinking microtubules toward poles Cell elongates as motor proteins push polar microtubules past each other

Begins when chromatids reach poles Microtubules disassemble Nuclear envelope reforms Chromosomes de-condense into chromatin

Cytokinesis begins before mitosis is complete Different in plants and animals Does not always take place

Contractile Ring Mechanism 1) a band of microfilaments of the cell cortex contracts 2) indentation forms : cleavage furrow 3) ring contracts until cell membrane is pinched in 2

Myosin motor proteins Move actin filaments Past each other to tighten ring

Cell Plate Formation Vesicles containing cell wall components move from golgi to equator Merging vesicle membranes form new cell membrane Cell wall components assembled in center of merging vesicles form new primary cell wall

Primary cell wall : flexible stretchy allows growth Secondary cell wall: deposited inside primary wall solid inflexible support wall

Interphase – time spent between cell divisions (90% of cell cycle) Mitosis – nuclear division Cytokinesis – cytoplasmic division

G1 – gap 1- cell grows ( max size based on.. SA:V ratio) cell performs its function for the body cell may never leave G1 (ex nerve cells) S – synthesis :entire genome is synthesized by semi-conservative replication Growth and cell function continue G2- gap 2 – cell grows & prepares to divide duplicates centrosomes & centrioles (not required: present in animals)

Controlled by activation of regulatory genes These genes code for regulatory proteins. Presence or Absence of these proteins determine if a cell moves on to the next phase of the cell cycle. Cell cycle regulatory proteins are called checkpoint proteins The genes that code for these proteins are checkpoint genes

Results from the failure of more than one checkpoint gene Which causes non-functional checkpoint protein Causes tumor development May cause cancer

CDKs are a type of Kinase that only functions when bound to cyclin. Cyclins are a class of checkpoint protein that activate enzymes by phosphorylation Different versions of cyclin activate different CDK enzymes that are needed for the cell cycle to proceed

Table 1 Cell cycle regulators and cancer Cyclin A 4 Complexed with CDK2 & 1 to regulate S phase &G2–M Overexpressed in breast & hepatocellular carcinoma Cyclin B1 Complexed with CDK1 to regulateG2–M Overexpressed in some breast carcinoma Cyclin D1 Complexed with CDK4/6 to regulate early G1 Overexpressed in multiple tumors Cyclin D2 Complexed with CDK4/6 to regulate early G1 Overexpressed in some colorectal cancers Cyclin E Complexed with CDK2 to regulate G1 & G1–S transition Overexpressed in multiple tumors including leukemias, carcinomas of the breast, colon, prostate

Inhibitors stop things CKIs stop the CDK enzymes from working Example: CKI p21 stops CDK2 from working…thus Stopping the transition from G1 – S phase The CKI inhibitor molecule p21 is only active when tumor suppressor gene p53 is transcribed (copied) *** know p53 ***

M-phase Promoting Factor = CDK-cyclin complex High enough concentration of MPF allows Cell to move from G2 into M phase MPF concentration reduced in Anaphase by breakdown of cyclin causing MPF to revert to inactive CDK MPF contains a CDK when activated by cyclin what does it do? phosphorylates other proteins

Growth Factors = proteins released by cells that cause nearby cells to divide *example of cell – cell communication* PDGF released by platelets cause Fibroblast(wound repair) cells to divide 1) PDGF binds to receptor on Fibroblast 2) signal transduction pathway initiated 3) cell passes G1 checkpoint and starts to divide

Cell Division limited by: 1) Density-dependent Inhibition cells that are crowded stop dividing 2) Anchorage dependency – cell must be anchored to extra-cellular matrix of a tissue to divide.

Cancer Cells NOT inhibited by density or anchorage CC do NOT stop dividing when out of Growth Factor CC do not follow signals of check point genes CC do not self-destruct by apoptosis

1 cell undergoes transformation (damage to DNA) Transformed cell avoids immune system avoids apoptosis ignores regular cell cycle signals uncontrolled cell division Benign tumor : cells stay anchored Malignant tumor cells spread = cancer Metastasis = spread of cancer cells

Mutation of Check Point Genes Change in chromosome number/structure Abnormal/irregular cell membrane lacks attachment proteins damaged signal/receptor proteins Secrete signal molecules that encourage blood vessel growth

Radiation for localized tumor Chemotherapy – poisons most damaging to dividing cells

1) G1 checkpoint – cycle initiation a)controlled by cell size b) growth factors c) environment 2) G2 checkpoint – transition to M a) DNA replication complete b) DNA damage/mutations 3) M-spindle checkpoint a) spindle attachment