Cell Structure Cell Biology

8/4/2019 Cell Structure Cell Biology

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CELL STRUCTURE



NUCLEUS

• Nucleus: The nucleus is the most obvious organelle inany eukaryotic cell. It is enclosed in a double membraneand communicates with the surrounding cytosol vianumerous nuclear pores. Within the nucleus is the DNA

responsible for providing the cell with its uniquecharacteristics. The DNA is similar in every cell of thebody, but depending on the specific cell type, somegenes may be turned on or off - that's why a liver cell isdifferent from a muscle cell, and a muscle cell is different

from a fat cell. When a cell is dividing, the nuclearchromatin (DNA and surrounding protein) condensesinto chromosomes that are easily seen by microscopy.



NUCLEOLUS

• The prominent structure in the nucleus isthe nucleolus. The nucleolus producesribosomes, which move out of the nucleus

and take positions on the roughendoplasmic reticulum where they arecritical in protein synthesis



CYTOSOL

• The cytosol is the "soup" within which allthe other cell organelles reside and wheremost of the cellular metabolism occurs.

Though mostly water, the cytosol is full ofproteins that control cell metabolismincluding signal transduction pathways,

glycolysis, intracellular receptors, andtranscription factors



CYTOPLASM

• This is a collective term for the cytosolplus the organelles suspended within thecytosol



CENTROSOME

• The centrosome, or MICROTUBULEORGANIZING CENTER (MTOC), is anarea in the cell where microtubules are

produced. Plant and animal cellcentrosomes play similar roles in celldivision, and both include collections of

microtubules, but the plant cellcentrosome is simpler and does not havecentrioles.



• During animal cell division, the centriolesreplicate (make new copies) and thecentrosome divides. The result is two

centrosomes, each with its own pair ofcentrioles. The two centrosomes move toopposite ends of the nucleus, and fromeach centrosome, microtubules grow into

a "spindle" which is responsible forseparating replicated chromosomes intothe two daughter cells.



CENTRIOLE

• Each centriole is a ring of nine groups offused microtubules. There are threemicrotubules in each group. Microtubules

(and centrioles) are part of thecytoskeleton. In the complete animal cellcentrosome, the two centrioles are

arranged such that one is perpendicular tothe other.



GOLGI APPARATUS

• The Golgi apparatus is a membrane-boundstructure with a single membrane. It is actually astack of membrane-bound vesicles that areimportant in packaging macromolecules for

transport elsewhere in the cell. The stack oflarger vesicles is surrounded by numeroussmaller vesicles containing those packagedmacromolecules. The enzymatic or hormonalcontents of lysosomes, peroxisomes and

secretory vesicles are packaged in membrane-bound vesicles at the periphery of the Golgiapparatus



LYSOSOME

• Lysosomes contain hydrolytic enzymesnecessary for intracellular digestion. Theyare common in animal cells, but rare in

plant cells. Hydrolytic enzymes of plantcells are more often found in the vacuole.



PEROXISOMES

• Peroxisomes are membrane-bound packets ofoxidative enzymes. In plant cells, peroxisomesplay a variety of roles including converting fattyacids to sugar and assisting chloroplasts inphotorespiration. In animal cells, peroxisomesprotect the cell from its own production of toxichydrogen peroxide. As an example, white bloodcells produce hydrogen peroxide to kill bacteria.

The oxidative enzymes in peroxisomes breakdown the hydrogen peroxide into water andoxygen.



SECRETORY VESICLES

• Cell secretions - e.g. hormones,neurotransmitters - are packaged insecretory vesicles at the Golgi apparatus.

The secretory vesicles are thentransported to the cell surface for release



CELL MEMBRANE

• Every cell is enclosed in a membrane, a double layer ofphospholipids (lipid bilayer). The exposed heads of thebilayer are "hydrophilic" (water loving), meaning that theyare compatible with water both within the cytosol andoutside of the cell. However, the hidden tails of the

phosopholipids are "hydrophobic" (water fearing), so thecell membrane acts as a protective barrier to theuncontrolled flow of water. The membrane is made morecomplex by the presence of numerous proteins that arecrucial to cell activity. These proteins include receptors

for odors, tastes and hormones, as well as poresresponsible for the controlled entry and exit of ions likesodium (Na+) potassium (K+), calcium (Ca++) andchloride (Cl-).



MITOCHONDRIA

• Mitochondria provide the energy a cell needs to move,divide, produce secretory products, contract - in short,they are the power centers of the cell. They are aboutthe size of bacteria but may have different shapes

depending on the cell type. Mitochondria are membrane-bound organelles, and like the nucleus have a doublemembrane. The outer membrane is fairly smooth. Butthe inner membrane is highly convoluted, forming folds(cristae) as seen in the cross-section, above. The cristae

greatly increase the inner membrane's surface area. It ison these cristae that food (sugar) is combined withoxygen to produce ATP - the primary energy source forthe cell



VACUOLE

• A vacuole is a membrane-bound sac that plays roles inintracellular digestion and the release of cellular wasteproducts. In animal cells, vacuoles are generally small.Vacuoles tend to be large in plant cells and play several

roles: storing nutrients and waste products, helpingincrease cell size during growth, and even acting muchlike lysosomes of animal cells. The plant cell vacuolealso regulates turgor pressure in the cell. Water collectsin cell vacuoles, pressing outward against the cell wall

and producing rigidity in the plant. Without sufficientwater, turgor pressure drops and the plant wilts.





ROUGH ENDOPLASMICRETICULUM

• Rough endoplasmic reticulum appears"pebbled" by electron microscopy due tothe presence of numerous ribosomes on

its surface. Proteins synthesized on theseribosomes collect in the endoplasmicreticulum for transport throughout the cell



RIBOSOMES

• Ribosomes are packets of RNA andprotein that play a crucial role in bothprokaryotic and eukaryotic cells. They are

the site of protein synthesis. Eachribosome comprises two parts, a largesubunit and a small subunit. MessengerRNA from the cell nucleus is moved

systematically along the ribosome wheretransfer RNA adds individual amino acidmolecules to the lengthening protein chain



CYTOSKELETON

• As its name implies, the cytoskeleton helps tomaintain cell shape. But the primary importanceof the cytoskeleton is in cell motility. The internalmovement of cell organelles, as well as celllocomotion and muscle fiber contraction couldnot take place without the cytoskeleton. Thecytoskeleton is an organized network of threeprimary protein filaments:

• - microtubules- actin filaments (microfilaments)- intermediate fibers



CELL CYCLE

• During development from stem to fullydifferentiated, cells in the body alternatelydivide (mitosis) and "appear" to be resting

(interphase). This sequence of activitiesexhibited by cells is called the cell cycle.

• Interphase, which appears to the eye to be a

resting stage between cell divisions, is actuallya period of diverse activities. Those interphaseactivities are indispensible in making the next

mitosis possible.



INTERPHASE

Interphase generally lasts at least 12 to 24hours in mammalian tissue. During thisperiod, the cell is constantly synthesizing

RNA, producing protein and growing insize. By studying molecular events in cells,scientists have determined that interphase

can be divided into 4 steps: Gap 0 (G0),Gap 1 (G1), S (synthesis) phase, Gap 2(G2). Gap 0 (G0): There are



G0 Phase

• Gap 0 (G0): There are times when a cellwill leave the cycle and quit dividing. Thismay be a temporary resting period or more

permanent. An example of the latter is acell that has reached an end stage ofdevelopment and will no longer divide (e.g.

neuron)



G1 Phase

• Gap 1 (G1): Cells increase in size in Gap1, produce RNA and synthesize protein.An important cell cycle control mechanism

activated during this period (G1Checkpoint) ensures that everything isready for DNA synthesis. (Click on the

Checkpoints animation, above.)



S Phase

• To produce two similar daughter cells, thecomplete DNA instructions in the cell mustbe duplicated. DNA replication occurs

during this S (synthesis) phase.



G2 Phase

• Gap 2 (G2): During the gap between DNAsynthesis and mitosis, the cell will continueto grow and produce new proteins. At the

end of this gap is another controlcheckpoint (G2 Checkpoint) to determine ifthe cell can now proceed to enter M

(mitosis) and divide



M Phase

• Cell growth and protein production stop at thisstage in the cell cycle. All of the cell's energy isfocused on the complex and orderly division into

two similar daughter cells. Mitosis is muchshorter than interphase, lasting perhaps onlyone to two hours. As in both G1 and G2, there isa Checkpoint in the middle of mitosis

(Metaphase Checkpoint) that ensures the cell isready to complete cell division. Actual stages ofmitosis can be viewed at Animal Cell Mitosis.

http://www.cellsalive.com/mitosis.htm

http://www.cellsalive.com/mitosis.htm



What is cell cycle?

• The cell cycle is required for cell growth and celldivision into two daughter cells. A eukaryotic cell cannotdivide unless it replicates its genome (DNA) and thenseparates the duplicated genome. To achieve these

tasks cells must perform DNA synthesis and mitosis.The cell cycle is an ordered set of events. The G1 phasestands for “GAP-1” and is required for cell growth andpreparation of DNA synthesis. The S-phase stands for“Synthesis” and replicates the genome. The G2 phase is

“GAP-2” and needed for cell growth and preparation for mitosis. The last phase is M and it stands for “Mitosis” inwhich cells segregate duplicated chromosomes





What is the Checkpoint?

• The cell cycle proceeds by a defined sequenceof events where late events depend uponcompletion of early events 1. The aim of the

dependency of events is to distribute completeand accurate replicas of the genome to daughtercells 2. To monitor this dependency, cells areequipped with the checkpoints that are set at

various stages of the cell cycle. When cells haveDNA damages that have to be repaired, cellsactivate DNA damage



• checkpoint that arrests cell cycle. According to the cell cyclestages, DNA damage checkpoints are classified into at least 3checkpoints: G1/S (G1) checkpoint, intra-S phase checkpoint,and G2/M checkpoint. Upon perturbation of DNA replication by

drugs that interfere with DNA synthesis, DNA lesions, orobstacles on DNA, cells activate DNA replication checkpoint that arrests cell cycle at G2/M transition until DNA replication iscomplete. There are more checkpoints such as Spindlecheckpoint and Morphogenesis checkpoint. The spindle

checkpoint arrests cell cycle at M phase until all chromosomesare aligned on spindle. This checkpoint is very important forequal distribution of chromosomes. Morphogenesis checkpointdetects abnormality in cytoskeleton and arrests cell cycle atG2/M transition.



What happens if you lose one ofcheckpoints?

• DNA replication and chromosome distribution areindispensable events in the cell cycle control. Cells mustaccurately copy their chromosomes, and through theprocess of mitosis, segregate them to daughter cells.The checkpoints are surveillance mechanism and

quality control of the genome to maintain genomicintegrity. Checkpoint failure often causes mutations andgenomic arrangements resulting in genetic instability.Genetic instability is a major factor of birth defects and in the development of many diseases, most notablycancer. Therefore, checkpoint studies are very importantfor understanding mechanisms of genomemaintenance as they have direct impact on theontogeny of birth defects and the cancer biology



DNA maintenance checkpoint

• Accurate duplication of eukaryotic genome is achallenging task, given that environment of cell growthand division is rarely ideal. Cells are constantly under thestress of intrinsic and extrinsic agents that cause DNA

damage or interference with DNA replication. To copewith these assaults, cells are equipped with DNAmaintenance checkpoints 3 to arrest cell cycle andfacilitate DNA repair pathways. DNA maintenancecheckpoints include (a) the DNA damage checkpoints

that recognize and respond to DNA damage, and (b) theDNA replication checkpoint



a) DNA damage checkpoint

• DNA damage checkpoints ensure the fidelity ofgenetic information both by arresting cell cycleprogression and facilitating DNA repairpathways. Studies on many different species

have uncovered a network of proteins that formthe DNA damage checkpoints. Central to thisnetwork are protein kinases of ATM/ATR familyknown as Tel1/Mec1 in budding yeast andTel1/Rad3 in fission yeast 4. These kinases

sense DNA damages and phosphorylatenumber of proteins that regulate cell cycleprogression and DNA repair pathways 3.



(b) DNA replication checkpoint

• Accurate replication of the millions or billions of DNAbase pairs in a eukaryotic genome is a remarkableachievement. This accomplishment is even moreastonishing when one considers for DNA synthesis arerarely ideal. Damaged template, protein complexes

bound to DNA, and poor supply of dNTPs are among themany obstacles that must be overcome to replicategenome. All of these situations can stall replicationforks. Stalled forks pose grave threats to genomeintegrity because they can rearrange, break, or collapsethrough disassembly of the replication complex 5. Thepathways that respond to replication stress are signaltransduction pathways that are conserved acrossevolution 6

• Atop the pathways are also ATM/ATR family kinases. These



Atop the pathways are also ATM/ATR family kinases. Thesekinases together with a trimeric checkpoint clamp (termed 9-1-1 complex) and five-subunit checkpoint clamp loader (Rad17-RFC2-RFC3-RFC4-RFC5) senses stalled replication forks andtransmit a checkpoint signal 3. One of major functions of

replication checkpoint is to prevent the onset of mitosis byregulating mitotic control proteins such as Cdc25. But perhapsthe most important activity of replication checkpoint is tostabilize and protect replication forks 8. The protein kinaseCds1 (human Chk2 homolog; in human, Chk1 is a functionalCds1 homolog) is a critical effector of the replication checkpointin the fission yeast Schizosaccharomyces pombe 9, 10. Cds1 isrequired to prevent stabilization of replication fork in cellstreated with hydroxyurea (HU), a ribonucleotide reductaseinhibitor that stalls replication by depleting dNTPs 11. In thebudding yeast Saccharomyces cerevisiae , a failure to activate

Rad53 (Chk2 homolog) is associated with collapse andregression of replication forks and gross chromosomalrearrangements in cells treated with HU 12-15.

•







• The Chk1 and Chk2/Cds1 checkpoint kinases, which arekey mediators of DNA damage and DNA replicationcheckpoints, are thought to be involved in cancerdevelopment 16. We found the Swi1 protein is requiredfor survival of replication fork arrest and effective

activation of Chk2 kinase in fission yeast. Swi1 formstight complex with Swi3 protein and moves withreplication forks. Swi1-Swi3 complex is also importantfor proficient DNA replication even in the absence ofagents that cause genotoxic stress, creating single-strand DNA gaps at replication forks 11, 17. Theseresults led us to propose Swi1-Swi3 define a replicationfork protection complex (FPC) that stabilizesreplication forks in a configuration that is recognized byreplication checkpoint sensors11, 17.



• Interestingly, Tof1 protein (Budding yeast Swi1homolog) has been reported to have similarfunctions. Tof1 is also involved in Rad53 (Chk2

homolog) activation and travels with replicationfork 18, 19. Tof1 is needed to restrain forkprogression when DNA synthesis is inhibited byHU indicating that Tof1 is required for

coordination of DNA synthesis and replisome (replication machinery) movement



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Cell Structure Cell Biology