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BioMed I First Test
Biomed fo Dental Hygiene
Question | Answer |
---|---|
Protons are... | positively charged located in the nucleus |
Neutrons are... | uncharged located in the nucleus |
electrons are... | negatively charged orbit the nucleus in shells, each shell contains 2,8 or 18 electrons when filled |
elements in the periodic table are arranged according to... | shell filling order |
atomic number equals... | number of protons an element is defined by its atomic number |
atomic mass equals... | number of protons plus number of neutrons |
valence electrons are... | electrons in the outer shell these are available for chemical reactions |
electronegativity measures... | atoms affinity for electrons |
elements with few electrons find it easier to | give up electrons to get a full outer shell |
elements with almost full shells find it easier to... | get more to fill up |
electronegativity does what on the periodic table | increases to the right on the periodic table |
what is the most electronegative element? | fluorine |
what is the octet rule? | atoms want their outer electron shells filled to 8 |
Ionic bonds are | when atoms give up or acquire an electron to fill a shell |
covalent bonds are | when atoms share electrons |
hydrogen bonds are | not really a chemical bond but a very strong charge interaction between electrons on one molecule with a proton on another |
What are examples of hydrogen bonding? | water as a solvent electrolytes |
electrons in a covalent bond spend more time orbiting... | the more electronegative nucleus |
synthesis | A+B--> AB |
Decomposition | AB-->A+B |
Transfer/Exchange | AB+CD-->AC+BD |
oxidation-reduction (redox) | A(-)+B-->A+B(-) |
exergonic reactions | electrons move to a lower energy state and the energy is release spontaneous give off energy in the process of happening |
endergonic reactions | electrons move to a higher energy state not spontaneous, must be coupled to an exergonic reaction reactions that take up energy in the process of happening |
coupling reactions | using the energy of an exergonic reactions to drive an endergonic one |
ATP has a high energy phosphate bond that is used to drive what reactions | endergonic |
Activation Energy: | the energy input required to get a reaction started |
What is reversible? | highly exergonic reaction reactions and products are close in energy low negative delta G |
What is irreversible | high negative delta G |
What happens in redox reactions? | custody of an election is physically transferred to a different atom along with its energy |
the less electron density associated with a carbon atom... | the more oxidized it is |
Factors increasing oxidation state of a carbon include | number of electrons shared with other atoms (how many bonds) electronegativity of the atoms sharing the bond (polarity) |
oxidation of glucose generates | ATP |
acid is the... | proton donor |
Base is the... | proton acceptor |
strong acids... | dissociate completely in water (reaction goes to completion) |
Weak acids... | dissociate part way (reaction is in equilibrium) |
Isotopes | atoms of an element are differentiated by their number of neutrons different atomic masses |
mole is.. | the mass of a compound in grams that is equal to its formula weight |
the molecule left after the proton is lost is called | a cognate base |
concentration is measured in | moles/liter=molarity |
pH scale is | concentration of H+ in a solution negative exponent turns logarithmic scale into linear measure of acidity |
buffers are | solutions of weak acid base pairs that act to maintain pH near their equilibrium pH point against the addition of other acids and bases |
ions in a solution is called | electrolytes |
all energy in an atom available for reaction is associated with... | the electrons |
exergonic reaction electrons | move to a lower energy state |
endergonic reaction electrons | move to a higher energy state |
catalyst... | lower the activation barrier to start reaction but does not change the energy yield |
oxidation states ethanol | ethanol-->acetaldehyde-->acetic acid |
oxidation states of the functional groups of carbon | alkane-->alcohol-->aldehyde (ketone)--> ester-->carboxylic acid |
when the pH is low, the hydrogen concentration is... | higher |
what are numbered as one in carbohydrates? | ketoses or aldoses with the carbonyl carbon |
what is the general formula for carbohydrates? | CnH2nOn |
what are the functions of carbohydrates? | main energy source for the body provides carbons for building core of the nucleic acids cell-cell interaction |
what are the simplest form of sugar taken in the diet | monosaccharides |
what must happen to all dietary sugars in order for them to enter metabolism? | be reduced |
what are some examples of monosaccharides | glucose, galactose, fructose |
glycosidic bond does what | joins carbon rings of two sugar monomers through oxygen |
why is the shape of disaccharides important? | recognition by the enzymes the break down these bonds for digestion |
sucrose is made up of what | glucose+ fructose alpha 1,2 bond |
lactose is made up of what | galactose+ glucose beta 1,4 bond |
maltose is made up of what | 2 glucose alpha 1,4 bond |
polysaccharides are | glucose joined by glycosidic bonds linkage determines superstructure of the polymer |
alpha linkage tend to favor what structure | coiled |
beta linkage tend to form what structure | fibrils |
branching determines what in polysaccharides | bushiness and thus hydration accessibility for enzymes |
what are the functions of polysaccharides | energy storage (glycogen, starch, dextran) structural rigidity (cellulose) |
glycogen is | alpha 1,4 bonds primary storage of glucose for animals in liver and muscle |
starch has two forms | amylose and amylopectin |
amylose is | unbranched |
amylopectin is | branched energy storage for plants |
dextran is | glucose monomers in alpha 1,6 linkage made by bacteria and secreted to form plaque. When calcified, this becomes calculus |
cellulose is | unbranched glucose in beta 1,4 linkage plants for cell walls to give structural rigidity glycosidic bonds are un-digestible to humans (fiber) |
general classes of lipids | long chain fatty acids, steroids, eicosanoids |
long chain fatty acids are | triglycerides (energy storage) phospholipids (membranes) |
steroids are | cholesterol and hormones |
general properties of lipids | mostly C and C atoms with very few electronegative atoms not water soluble, hydrophobic |
roles of lipids in body | energy storage membrane structural components hormones |
structure of fatty acids | long hydrocarbons chains with a carboxylic acid group on the end |
saturated is | when all carbons in the chain (except carboxyl) are fully reduced saturated with hydrogens |
unsaturated is | fatty acid contain one or more double bonds |
cis bond does what | puts a kink in the molecule |
trans double bond does what | makes straighter molecule more like the unsaturated one |
adding double bond to fatty acids... | increases the melting point by disrupting the packing of the chains with kinks example: butter and lard (solid at room temp) |
fatty acids with trans double bonds like trans fat... | have a higher melting point |
essential fatty acids are what | fatty acids that your body needs but cannot make on its own such as omega 3 and omega 6 fatty acid |
triacylgycerols are composed of | fatty acid chains connected to glycerol by ester linkages with their carboxyl groups |
triglycerides are most concentrated form of energy storage in the body because | more reduced bonds stored in adipose tissue |
structure properties of cholesterol | 4 ring structure with a hydroxyl on one end and a hydrocarbon tail hydrophobic but hydroxyl is the only polar bond in the molecule |
what is a major lipid component of membrane | phospholipids |
phospholipids are like triacylglycerols except that... | the third fatty acid is replaced with a phosphate linked to a charged group (most often choline) |
amphipathic | part of it is hydrophobic and part is hydrophilic |
what makes phospholipids amphipathic? | charged group |
cholsterol is weakly amphipathic because | the OH on the outward membrane |
cholesterol also interrupts phospholipid packing and makes it.. | more fluid |
dehydration synthesis... | produces water connects disaccharides |
hydrolysis | breaking with water |
ester | two carbons jointed by an oxygen |
bond between two sugar monomers | glycosidic bond |
does cellulose have branching? | no |
body doesn't make what kind of fatty acids? | cis fatty acids |
fats can be packed in better than carbohydrates because | they are not hydrated like carbohydrates are |
ribose is present in | RNA |
deoxyribose is present in | DNA |
nucleic acid structure contains | pentose sugar (RNA or DNA) Phosphate Base (Guanine, Adenine, Cytosine, Thymine (Uracil)) |
roles of nucleic acids | storage and propagation of genetic information (DNA) Messanger of genetic information (RNA) Energy for Chemical reactions (ATP) |
what drives endergonic reactions in the cells? | hydrolysis of the terminal bond in ATP fatty acid synthesis for energy storage |
which part of ATP contain highly reactive because of so much electron density in close proximity | phosphorous and oxygen |
what are the four bases that contain the genetic code | G, A, T, or C |
double helix contains | sugar- phosphate backbone forms the helix bases point into the center and hydrogen bond with the facing bases on the opposite helix |
differences between RNA from DNA | Sugars have a hydroxyl at the 2' carbon instead of an H cannot form double helix less stable than DNA, intended to be carriers |
what happens in transcription | DNA unwinds and a polymerase enzyme makes a base paired copy of the sequence but using ribonucleotides |
what happens in translation | the RNA binds to the ribosome complex and an amino acid chain is constructed based on the sequence of the three base codons in the RNA |
what are the roles of proteins | structural proteins globular proteins |
what are the structural proteins | keratins (hair and skin) and collagens (connective tissue) cytoskeleton (actin, microtubules) |
what determines the type of amino acid | the side chain |
what is the structure of amino acids | central carbon, amino, carboxyl and side chain |
peptide bond is formed when | amine of one amino acid binds to the carboxyl of another ester with a nitrogen instead of an oxygen |
what is primary structure | the sequence of amino acids in the polypeptide chain |
what is secondary structure | the folding of the chain into alpha helix, beta sheet, collagen triple helix |
what is tertiary structure | folding into the 3-D structure of the molecule |
what is Quaternary structure | packing of different polypeptide subunits together to make a finished product (subunits are not covalently linked) |
what is an active site? | pocket that the substrate fits into to undergo a chemical reaction |
nucleoside is | sugar+ base |
nucleotide is | sugar+ base+ phosphate Nucleoside+phosphate |
reactants are also known as... | substrates |
DNA-->RNA is what | transcription happens in nucleus |
RNA--> protein is what | translation happens in cytoplasm |
thymine is used in... | DNA |
Uracil is used in... | RNA |
RNA can have structural roles such as | transfer RNA |
cytology is | the study of cell structure |
cell physiology is | the study of cell function |
the cell is divided into three main parts... | plasma membrane, cytoplasm and nucleus |
cytosol is... | fluid portion of the cytoplasm |
cytoskeleton is... | network of protein tubules and filaments |
cytoplasm consists of | cytosol, cytoplasm, nucleus |
the plasma membrane is what | Forms the cell’s flexible outer surface, separating the cell’s internal environment (everything inside the cell) from the external environment (everything outside the cell). |
fluid mosaic model means | membrane resembles a continually moving sea of fluid lipids containing a mosaic of proteins |
what is the structure of the plasma membrane | lipid bilayer and membrane proteins |
lipid bilayer is... | basic structural framework of the plasma membrane lipid molecules are amphipathic made up of phospholipids, cholesterol and glycolipids |
what is the percentage of phospholipids? | 75% |
what is the percentage of cholesterol? | 20% |
what is the percentage of glycolipids? | 5% |
polar head in lipid bilayer is | charged, hydrophilic faces outward to the watery substance |
nonpolar tail in bilayer | hydrophobic faces inward forming hydrophobic region of the bilayer |
what constitutes membrane proteins? | integral membrane proteins peripheral membrane proteins |
phospholipids are | lipids that contain phosphorus phosphate containing part is polar head two long fatty acid chains are nonpolar tails |
cholesterol is | found in both layers of bilayer stabilizes membrane and influences membrane fluidity |
cholesterol contents (polar head and nonpolar tails) | tiny OH group polar head stroid rings and hydrocarbon chain nonpolar tail |
glycolipids are | carbohydrate moiety attached to phospholipid heads found only in the membrane layer that faces extracellular fluid and causes bilayer asymmetry |
glycolipids contents (polar head and nonpolar tail) | carbohydrate moiety- polar head two fatty acid chains- non polar tail |
integral proteins are | extend into or across the entire lipid bilayer, Firmly embedded into the membrane bilayer and are amphipathic |
transmembrane proteins are | integral proteins that project on both sides of the membrane (cytosol and extracellular fluid) some integral proteins are glycoproteins |
peripheral proteins are | located on the inner (cytoplasmic) or outer (Extracellular surface of the membrane |
glycocalyx is | carbohydrate protions of glycolipids and glycoproteins forms an extensive sugary coat |
glycocalyx functions | cell recognition cell adhesion cell protection (from enzyme digestion) |
ion channels are | pores that allow specific ions to flow through to enter or exit the cell formed by integral proteins |
carriers are | transporters integral proteins that bind a specific substance, change their shape and move it across the membrane |
receptors are | integral proteins that recognize and binds to a specific type of molecule called a ligand |
ligand is | a specific molecule that binds to a receptor |
enzymes are | integral and peripheral proteins that catalyze specific chemical reactions |
linkers are | integral and peripheral proteins that anchor proteins to one another in plasma membrane and anchor proteins to protein filaments |
cell identity markers are | membrane glycoprotein and glycolipids that allow a cell to recognize other cells of the same kind |
lipids and proteins seldom do what | flip flop from one half of the bilayer to the other |
membrane fluidity depends on | number of double bonds (kinks) in fatty acid tails of the lipids amount of cholesterol |
double bonds do what to membrane fluidity? | increase |
what does cholesterol do to membrane fluidity? | cholesterol stabilizes the membrane and influences fluidity decreased fluidity at normal body temperature increased fluidity at low body temperature |
lipid bilayer is permeable to... | nonpolar, uncharged molecules oxygen, carbon dioxide and steroids |
lipid bilayer is slightly permeable to... | small, uncharged polar molecules water and urea |
lipid bilayer is impermeable to... | ions and charged or polar molecules glucose |
macromolecules are unable to pass through the plasma membrane except by... | vesicular transport |
what is a vesicle? | a membranous sac formed by budding off from an existing membrane |
endocytosis is... | materials move into a cell in a vesicle formed from the plasma membrane |
what are the types of endocytosis | receptor mediated endocytosis phagocytosis pinocytosis |
receptor mediated endocytosis is | selective uptake of large molecules and particles requires the binding of a ligand to its specific receptor in the plasma membrane |
phagocytosis | ingestion of solid particles (worn out cells, whole bacteria or viruses) from the extracellular compartment cell eating another form of receptor mediated endocytosis |
endocytosis is | ingestion of fluid from the extracellular compartment cell drinking NO receptors involved |
exocytosis is | materials move out of a cell by the fusion of a vesicle with the plasma membrane vesicle formed inside the cell containing materials to be released from the cell |
trascytosis is | materials are taken up via endocytosis on one side of the cell transported across the cell in a vesicle and then released via exocytosis on the opposite side of the cell |
cytosol is composed of | water, proteins, carbohydrates, lipids and inorganic substances |
microfilaments are | most are composed of actin function in movement provide structural support form core of microvilli |
intermediate filaments are | several different proteins form them provide structural support anchor organelles "tonofilaments" of desmosomes |
microtubules are | long, unbranched hollow tubules grow out from an organizing center called centrosome in nondividing cells composed of protein tubulin |
what are the functions of microtubules | help determine cell shape intracellular transport of organelles migration of chromosomes during cell division by "spindle apparatus" form core of cilia and flagella |
centrosome are | located near the nucleus, consisting of a pair of centrioles and pericentriolar material serves as an organizing center for formation of mitotic spindle in cell division |
centrioles are | non membrane limited organelles a pair of centrioles arranged at right angles 9+0 arrangement of microtubule triplets |
cilia are | short, hair like projections of the plasma membrane, many per cell, motile contains a core of 20 microtubules surrounded by a plasma membrane anchored to a basal body |
axoneme is | 9+2 arrangement of microtubules cilia |
what are the functions of cilia | move material across cell surface |
flagella is | similar in structure to cilia usually one per cell propel entire cell- like sperm |
ribosomes are | sites of protein synthesis, found freely in the cytoplasm consists of a small and large unit (made separately in nucleolus and assembled in cytoplasm) |
polyribosomes are | several ribosomes attached to the same messenger RNA function in synthesis of proteins used within the cell |
rough endoplasmic reticulum | continuous with nuclear membrane outer surface attached with ribosomes function in synthesis of proteins that will be transported into the goli complex for further modification |
smooth endoplasmic reticulum | extends from rough endoplasmic reticulum outer surface has NO ribosomes attached to it |
what are the functions of smooth endoplasmic reticulum | lipid metabolism and absorption steroid synthesis drug detoxification calcium uptake and storage (muscle tissue) membrane formation |
cisternea are | membranous sacs with bulging edges |
cis face of golgi complex | convex, forming face faces the rough endoplasmic reticulum |
medial cisternae of golgi complex | cisterneae between cis and trans face |
trans face of goli complex | concave, maturing face faces the plasma membrane |
golgi complex function | receives newly synthesized proteins from rough endoplasmic reticulum via transport vesicles sort and package proteins into vesicles for transport to different destinations |
extracellular environment destination from goli complex | secretory vesicles |
plasma membrane destination from goli complex | membrane vesicles |
other organelles destination from goli complex | transport vesicles |
lysosomes are | intracellular vesicles formed from goli complex contain hydrolytic enzymes- function in digestion |
heterophagy is | digestion of phagocytosed extracellular materials bacteria |
autophagy is | digestion of intracellular organelles worn out mitochondria |
autolysis is | cellular self digestion |
lysomes are made in the ______ and packed in the ______ but remain within the cell | rough endoplasmic reticulum golgi |
peroxisomes are | similar in structure to lysomoes contain oxidative enzymes- oxidases remove hydrogen atoms from various organic substances |
mitochondria function | production of high energy compounds ATP cation buffer for cytosol |
mitochondrial matrix is | central fluid filled cavity enclosed by inner membrane DNA, RNA, ribosomes, mitochondrial granules |
nuclear envelope is | double membrane outer membrane continuous with rough endoplasmic reticulum perforated by water filled nuclear pores |
nucleolus is | one or more per cell not surrounded by a membrane consists of DNA, RNA and protein site of ribosome synthesis |
chromosome is | consists of a long DNA molecule coiled together with histone proteins carries the cell's hereditary units called genes |
chromosomes exist as what in non dividing cells | chromatin |
euchromatin are what | DNA strands uncoiled for transcription |
heterochromatin are what | DNA tightly packed |
once separated, the chromatids become... | chromosomes |
each somatic cell has how many pairs of chromosomes | 23 |
gene is | the entire nucleic acid sequence that is necessary for the synthesis of a functional gene product |
gene product is | polypeptide (protein) or RNA |
Gene expression | a gene's DNA is used as a template for synthesis of a specific protein involves transcription and translation |
transcription happens in | nucleus |
translation happens in | cytoplasm |
RNA polymerase | catalyzes transcription |
promoter is | a specific nucleotide sequence located near the beginning of a gene determines the transcription start site |
terminator is | a specific nucleotide sequence located near the end of a gene specifies the transcription stop site |
exons are | nucleotide sequence that code for parts of a protein |
Introns are | nucleotide sequence located between exons that do not code for parts of a protein |
pre mRNA in transcription are | contains information from both introns and exons |
RNA splicing in transcription are | removes intronic RNA segments and joins exotic RNA segments (functional mRNA) catalyzed by an enzyme called small nuclear ribonucleoproteins |
transcription, what happens | genetic information encoded in double stranded DNA is copied into a single stranded RNA molecule Only one of the two DNA strands serves as a template for RNA synthesis |
translation, what happens | the process of reading the mRNA nucleotide sequence to determine the amino acid sequence of the protein |
genetic code is | set of rules that relate the nucleotide sequence of a gene to the corresponding nucleotide sequence of mRNA and then to the amino acid sequence of a protein |
codon | a group of three consecutive nucleotides in RNA |
RNA had how many nucleotides | 4 |
proteins have how many amino acids | 20 |
tRNA is what | clover leaf like structure, one end carries a specific amino acid, the opposite end consists of a triplet of nucleotides |
messenger RNA | directs the synthesis of a protein |
ribosomal RNA | joins with ribosomal proteins to make ribosomes |
transfer RNA | binds to an amino acid and holds it in place on a ribosome until it is incorporated into a protein |
gene mutations are | permanent changes in the DNA nucleotide sequence of a gene |
the reactants on which an enzyme acts are called | substrates |
induced fit is | substrates enter the pocket moves to hug them and hold them in the right orientation |
cofactors are | small molecules or ions needed in the active site to perform a reaction when the amino acid side chains are not enough |
cofactors are obtained from where? | the diet |
reversible inhibition is | competitive, non competitive |
competitive inhibition is | an inhibitor that looks like the substrate fills up the active site and prevents substrate from entering |
non competitive inhibition is | an inhibitor binds to another part of the enzyme causing a conformational shift that ripples through the molecule to mess up the active site so it is less able to perform the reaction |
irreversible inhibition is | suicide inhibitor |
suicide inhibitor is | an inhibitor masquerading as a substrate covalently attaches to the active site penicillin |
allosteric activation | binding of an activator to a remote site of the enzyme that causes the active site to be an even more efficient catalyst (reverse of non competitive inhibition) |
enzyme mutations are | mutations in enzymes that alter their function or loss of them all together, disrupts reactions PKU |
cofactor deficiencies are... | dietary deficiency of required cofactors causes enzyme malfunction scurvy |
collagen requires what | hydroxylation of prolines to form the collagen triple helix neds ascorbate cofactor (vitamin C) |
what enzyme in bacteria is required to form cross links in cell wall synthesis | transpeptidase |
methotrexate does what? | kills fast dividing cells that need increased DNA synthesis treats cancer |
dihydrofolate reducatese is required for | thymine required for DNA synthesis |
iron is not a... | coenzyme |
heme and iron are... | cofactors |
transcription occurs in the.. | nucleus |
translation occurs in the.. | cytoplasm |
transcription is catalyzed by... | enzyme called RNA polymerase |
what is a promoter? | a specific nucleotide sequence located near the beginning of a gene determines the transcription start site |
what is a terminator? | a specific nucleotide sequence located near the end of a gene specifies the transcription stop site |
what is an exon? | nucleotide sequence that code for parts of a protein |
what is an intron? | nucleotide sequence located between exons that do not code for parts of a protein |
define translation | the process of reading the mRNA nucleotide sequence to determine the amino acid sequence of a protein |
what is genetic code? | a set of rules that relate the nucleotide sequence of a gene to the corresponding nucleotide sequence of mRNA and then to the amino acid sequence of a protein |
what is a codon? | a group of three consecutive nucleotides in RNA |
translation occurs on what? | the ribosomes |
what are the three types of RNA? | messenger RNA Ribosomal RNA Transfer RNA |
what is messenger RNA? mRNA | directs the synthesis of a protein |
what is ribosomal RNA? rRNA | joins with ribosomal proteins to make ribosomes |
what is transfer RNA? tRNA | binds to an amino acid and holds it in place on a ribosome until it is incorporated into a protein |
what is a somatic cell? | any cell of the body other than a germ cell they are diploid (contain double sets of DNA) one member of chromosomes from each parent |
what is germ cells? | gamete (sperm or egg) or any precursor cell destined to become gamete haploid cells, one set of chromosomes |
what is mitosis? | somatic cell division: one parent cell gives rise to 2 identical daughter cells nuclear division and required for tissue repair and growth |
what is meosis? | reproductive cell division produces gametes (sperm or oocyte), occurs in testes and ovaries |
what happens during interphase? | parents cell duplicates its 23 pairs of chromosomes and cellular organelles |
what happens during mitotic phase? | parent cell divides in two identical daughter cells |
Inter phase consists of what? | G1, S, and G2 parts |
what happens during G1 phase? | cells metabolically active, duplicates organelles and cytosolic components starts replicating centrosomes |
what happens during S phase? | DNA is replicated two identical DNA molecules formed from each original DNA molecule |
what happens during G2 phase? | cell growth continues enzymes and other proteins are synthesized and replication of centrosome is completed |
how long is G1 phase? | 8-10 hours |
how long is G2 phase? | 4-6 hours |
how long is S phase? | 6-8 hours |
cytokinesis is | cytoplasmic division division of cytoplasm and organelles |
what is a benign tumor? | a tumor that does not metastasize or spread may be harmless |
what is a malignant tumor? | cancer has the ability to undergo metastasis and often fatal |
what is metastasis | the spread of cancerous cells to other parts of the body |
key behaviors of cancer cells are | proliferate rapidly and indefinitely= out of control invade surrounding normal tissue matastasis= detach from primary tumor and invade elsewhere do not kill themselves by apoptosis |
what are the environmental risk factors that increase incidences of cancer? | carcinogens, oncogenic viruses |
carcinogens are... | chemical substances or radiation that causes cancer (radiation or cigarettes) |
oncogenic viruses are | viruses that cause cancer |
carcinogens induce mutations in proto-oncogenes and convert them to... | oncogenes |
what are oncogenes? | cancer causing genes derived from proto-ongogenes have the ability to turn a normal cell into a cancerous cell |
proto-ongogenes are | encode proteins that regulate normal growth and development become oncogenes when they are mutated or inappropriately activated |
dominant mutations are... | only one gene copy needs to be mutated |
activating mutations are | gain of function- the oncogene product are more active in stimulating cell survival and proliferation |
what are tumor suppressor genes? | produce proteins that normally inhibit cell division |