Bio 1001a midterm 1

Cycles 2-5

explain: perspectives relating to life

• issues choosing one

• Indigenous

• Artistotle

• NASA definition

• finding a concept that is universal; make sense for both scientists and non-scientists (applicable across disciplines)

• Indigenous: emphasize the interconnectedness and reciprocity of all living things, beyond what science considered living

• Aristotle: something that grows, is self sustaining and reproduces…..includes the concept of the cell being a universally accepted characteristic of life

• NASA definition: a self sustaining chemical system capable of Darwinian evolution…bring in molecules from the surronding and use energy to transform those molecules into different forces necessary for life

explain whether or not viruses should be considered “life”

• lack their own metabolism..by NASA def. are not self sustaining

• dont undergo cell resp or synthesize their own proteins

• cant complete their lifecycle without invading living cells (needs the ribosomes to make proteins bc it can’t itself)

• but they do have nucleic acis and replicate

• can evolve through natural selection

define

entity

includes a wide range of sel replicating and evolving systems (viruses, computer programs)

define

organism

forms of life that posses five core characteristics

5 core characteristics of life

1. comprised of cells : cell is the fundamental unit of life

2. harness energy and matter: all forms of life acquire energy and matter form the env and use them to maintain their highly ordered state

3. reproduce and grow: organisms reproduce giving rise to offspring that grow and develop into adults

4. respond to stimuli: organisms can make adjustments to their structure, function, and behavior in response to changes to the external env

5. evolve: populations of living organism change over the course of generations to become better adapted to their environment

define

cell

• smallest unit of life

• cant have life without cell and the other way you get a new cell is by an older cell dividing by two

• cells can look very different (different environments and roles)

core features of a cell (3)

+types of organelles

• plasma membrane

• organelles that are universal (ribosomes)

• organelles that are cell specific (nuclei, chloroplasts, mitochondria)

how are organisms thermodynamically open systems?

• constantly bringing in energy and matter from their surrounds and releasing other forms of energy and matter back into the environment

• energy is just required to maintain the highly ordered state required to stay alive

ie. DNA, proteins, membrans are constantly breaking forna nd new ones are bein made using the matter and energy cells bring in from the outside

explain

reproduction

+inheritance

• parental organisms produce offspring

• parents pass copies of their DNA to their offspring

• inheritance: transmission of DNA (genetic information) from one generation to the next

explain

cell cycle in terms of growth

• an increase in organism size is the result of an increase in the size of individual cells along with an increase in the number of cells (cell division)

• growth is a process of development; series of programmed changes encoded in DNA (move from embryonic state to maturity)

explain

life responding to stimuli

+homeostasis

• organisms can make adjustments to their structure, function and behavior in response to changes to the external env

• organisms has to sense a change in env

• homeostasis: goal is to maintain a relatively constant internal state to compensate for when external conditions change

explain

evolution in terms of a characteristic of life

+effects of natural selection

+evolutionary adaptation

• evolution is a trait that is only true of a population of individuals or a particular specific (not just one organism)

• evolutionary adaptation: natural selection allows the population as a whole to be able to grow and reproduce better in a particular env over many generations

• changes in gene structure and function and the development of novel traits, and can lead to the emergence of new species

define

natural selection

• random mutations to DNA result in offspring within a population being better able to survive and reproduce than others, leading to a population expressive the favorable trait in a greater proportional with each passing generation

explain

cell theory

• all living cells arise only from the growth and division of other pre-existing living cells

4 marcomolecules all organisms are composed of

• nucleic acids

• proteins

• lipids

• polysaccharides

define

abiotic syntehsis

• synthesis of organic molecules in the absence of life

building blocks of complex biological molecules (4)

• amino acids (building blacks of proteins)

• fatty acids (component of lipids)

• purine and pyrimidine nucleotides (components of nucleic acids

• range of sugars such as riose, glucose, fructose

why are viruses not necessarily bad

• viruses play vital ecological roles and have valuble applications in human health

• ecologically, viruses relate microbial populations, influence nutrient cycling, maintain ecosystem balance and enhance genetic diversity through horiontal gene transfer

• we can harness their genetic material fo =r various purposes (gene theorapy to treat cancer adn other conditions)

why are viruses classified as infectious biological particles rather than organisms

• cannot reproduce on their own

• lack metabolic system to provide energy for their own life cycles; depend on host cell that they infect for these functions

• does not have cytoplasm enclosed by a plasma membrane (like all known organisms)
  
  

strucutre of a virus

+capsid

+envelope

• one of more nucleic acid molecules surrounded by a protein coat (capsid)

• some capsid can be enclosed in a membrane (envelope)

explain

viruses nucleic acid genome (5)

• either DNA or RNA

• can be composed of either single strand or double stand

• all viruses have genes that encode at least their coat proteins as well as proteins involved in regulation of transcription

• genomes of enveloped viruses also include genes required for the sysnthesis of envelope proteins

• some have virus specific enzymes for nucleic acid replication
  
  

explain

helical viruses

• protein subunits assemble in rod-like sprial around the genome

• ie. viruses that infect plants

• cab be enveloped in a membrane from the hosts membrane (like polyhedral)
  
  

explain

polyhedral viruses

• coat proteins form triangular units that fit together like the parts of a soccer ball

• can infect animals, plants and bacteria

• in some, protein spikes that provide host cell recognition extend from the corners, where the facets fit together

• can be enveloped with membrane from host membrane (like helical)
  
  

explain

enveloped viruses

• whatever virus type, now its just enveloped in the host cell’s membrane

• proteins synthesized from the viral genome in the host cell are transported to and embedded in the membrane before the virus particle buds through the host cells

• …these proteins are important for recognition and binding to host cells

why is the ane. of a vrisu not the same as the disease it causes

• while viruses themselves are trasmitted from host to host, the disease is a manifestation of the bodys reponse to the viral infection

• ie. HIV virus leads to AIDS

how are viruses classified

• using critera such as virus size, strucutre, genome structure (DNA or RNA, single stranded or double stranded) and how theri nucleic acid is replicated

what do viruses usually infect (2)

• a single specifies or a few closely related species

• may even infect only one organ system or s single tissue or cell type in its host

how come some viruses arent pathogens

• benefit their hosts

• infect by a non pathogenic virus protects human hosts against pathogenic viruses

• ininfere with replication or other functions of pathogenic viruses

• act to defend their host cell

how to viral particles move

random molecular motions until they contact the surface of a host cell

how to viruses infect host cell

• virus or viral geno0me must enter the cell’

• inside the cell the viral genes are expressed, leading to replication of the viral genome and assembly of pregeny viruses

• virons: new virus particles are the new, complete, extracellular form of the virus

• virons are released from the hot cell, usually killing the host cell in the process

explain

viruses infecting animal cells (2)

• follow similar pattern to viruses for bacterial cells but but both the viral coat and the genome enter the cell

• depending on the virus, removal of the coat to release the genome occurs during or after cell entry (envelope does not enter the cell

how do viruses without an envelope enter a host cell

• bind by their recognition proteins to the plasma membrane and then are taken into the host cell by endocytosis

how do enveloped viruses enter the host cell (2)

• virus coat and genome enter the host cell plasma membrane

• other ones enter host cells by endocytosis

define

spike proteins (S proteins)

• they have two parta S2 and S2

• S1: top portion that binds to the receptor on the host cell

• S2: transmembrane portion that participate in the fusion of the viral envelop with the host membrane

define

nucleocapsid

• the combination of the capsid and the viral nucleic acid

three mechanisms by which the virus shuts down the hosts cell’s translation (reduces competition)

1. protein are produces that seek out and neutralize mRNAs that do not have a viral tag

2. channels are blocked to prevent host mRNA from moving from the nucleus into the cytoplasm

3. the prevention of mRNA from reaching the cytoplasm also means that proteins that would alter the immune system are not produced

define

retro virus

• two copies of singel stranded RNA

explain the HIV replication cycle

how does HIV infect the cell

• can access cells nucleus and integrate its genome into the hosts nuclear genome

• second strand of DNA is synthesized using the first strand as a template

define

asymptomatic

+example w virus

• does not benefit the virus to harm the host

• mostly animal viruses

how do pathogenic viruses cause diseases

• cause cell death when progeny viruses are released from the cell (massive cell death, destorying vital tissues or causing leasions in membranes/skin)

• other release cellular molecules when infected clls break down, which can induce fever and inflammation

• other viruses alter gene function when they insert into the host cell DNA, leading to cancer and otehr abnormalities combating

characteristics of plant viruses (4)

• rodelike or polyhedral

• most contain RNA as their nuclic aci, some have DNA

• due to the protective nature of cell wall, they access plant cells through mechanical injuries (tramistted from one plant to another during pollination or herbivorous animals)

• tramission can also occur from one genenration to the next in seeds

how do plant viruses act inside a cell

• mostly replicate like animal viruses

• virus particles can pass from infected to healthy cells through plasmodesmata, the opening in cell walls that interconnect the cytoplasm of plant cells, and through the vascular system

how are plant viruses classified

• by the type of plant they infect and tehir most visible effects

why are viral infection difficult to treat (4)

• viruses are “hidden” inside host ells and use host cell machinery to replicate

• there are often no obvious viral products to be targeted by drugs

• unaffected by antibiotics and other treatment methods for bacterial infections

• many viral infections are allowed to run their course… with treatment limiting to releiving symoptoms while the natural immune defences of the patient atack the virus

• orrr vaccine development for really deadly viruse
  
  

why do we need new flu vaccines every year (4)

• genome consists of eight seperate pieces of of RNA

• when two different fly viruses infect the same person, the RNA segments can assemble in random combinations derived from either parent virus

• new combos change protein coat of the virus, making it unrecognizable to antibodies developed againt either parent virus

• random mutations in RNA genome of the viruys add to the variations in the coat proteins that make previously formed antibodies defective

Hep C/AIDS treatment case study: how does it work

• it helps suppress the virus’s replication, reduce viral load in the bloodstream to undetectable levels and prevetn progression to AIDS

• made of a bunch of inhibitors that block the various stages of the viral life cycle

• doesnt cure but helps individuals to live longer

why is the effort to control viruses from animals so complicated? (3)

• dealing with viruses that have broad host specificty and can infec other animal in addition to humans

• since other animals can harbour these viruses, we can never succesfully eradicate the diseases they cause

• also, as human invade animal habitat, animals mutate and make virus mutate with them and then even badder

origins of virus hypothesis (fragments) (4)

+explain the process of fragments of genetic material into virus and incliude evolution

• viruses can duplicate only by infecting a host cell (probably evolved after cell appeared)

• may rep “escaped” fragments of DNA molecules that once formed part of genetic materia of living cells or an RNA copy of such a fragment

• the fragments first became surrounded by a protective layer of protein with recognition functions and then these fragments escaped their parents

• as it evolved, info encoded in the core of thevrius became reduced to a set of diretions for producing more viral particles of the same kind
  
  

origins of virus hypothesis (ancient) (2)

• viruses are very ancient

• virus like particles predating the first cell an=d originating in the “primordial gene pool” - pool of RNA that is thought to have been the first genetic material

viruses and their evolution (4)

+common ancestor

+impact on evolution of cell life

+benefit to genetic material

+eukaryotic life…

• they do not have one common ancestor (cannot draw phylogenetic tree)

• they play an important role in the evolution of cellular life becuase of their ability to integrate their genes into their hosts and to aquire genes from their hosts

• can also provide new genetic material (new enzymes and other proteins)

• evolution of eukaryotic cells…nucleaus originating from a large, double straded DNA virus that infected prokaryotic cells= eukayotic cell

define

evolution

• gradual change of populations of organisms over time

how does evolution explain diversity (3)

• underlying common features that organisms posess

• enoumous diveristy of life on earth

• so many forms…one common ancestor

• understanding of evolution helps in understanding how species continue to change over time in response to environmental changes or challenges (antibiotics in case of bacteria, pollution, deforestation, climate change)

define

process of evolution

+mechanism that drives evolution

• descent with modification

• natural selection

explain

natural selection

+4 conditions for evolutions through natural selection

• occurs when differential survival and reproduction of individuals with particular traits in a population lead to changes in the genetic makeup of the population over generations

1. the trait must be heritable

2. genetic variation in the trait must exist in the population

3. there must be differential survival and reproduction of individuals with different versions for the trait based on environmental factors

4. more offspring must be born than can survive

explain natural seleciton

effect of environmental factors

• limited food or habitat avalibility, disease….can reduce ability of individual organisms to survive/reproduce

• organisms with certain traits/characteristics may be able to overcome or tolerate differnt environmental conditions better thank

explain

evolution in terms of traits being passed on

• difference result from changes in their DA and thus can be inherited

• organisms with heritable traits that allow them to outcompete for limited resouces, or to avoid predation or disease will increase their rates of survival and reproduction and leave more offspring

• individuals in population without those traits are less likelu to reproduce, leaving fewer, if any, offspring

• the advantageous heritable traits will become more common in the next generation

individuals with certain hertiable traits are more likely to survive ad reproduce reprodce than other individuals, leaving to population level changes

explain

selective breeding

• humans can select which of the crops, anismals or whatever to breed with the best traits (bigger corn, sweeter fruit, cuter dogs with less health problems)

• these beings are selectively bred by humans to have the best outcome…not technically natural selection

define

population

+generation

connection between them

• a group of interbreeding individuals of a species that life together in a specific space

• the time period over which evolution acts

the differental reproduction of individuals in a population over many genrations leads to population-level changes in the expression of certain heritable trait

define

endemic species

+Galapagos mockingbirds

species found nowhere else on earth

• four species of mocking bird on the Galapagos islands

• each of these mockingbirds have morphologically distinct traits…but the four species have underlying general similarities, indicating that the four species all diverged from a common ancestral population

• 
  
  

  

this is an example of decent with modification

define

adaptation

+connection to differential survival and then natural selection

-the inherited aspects of an individual that make it well suited to thrive in a particular environment

• from generation to generation, with differential survival and reproduction, a population can become better adapted to a specific environment because of natural selection

define

fitness

• individuals with the set of traits that lead to greater survivorship ad reproductive success are said to be more fit than others

• the term describes an individuals reproductive success

• an orgfanism has higher fitness than another if it leaves more ofpsring, in turn, survive to reproduce

3 aspects crucial to fitness

1. fitness is a relative concept (doesnt matter in absoluite terms how many offspring an individual leaves, only that ut leaves more than others)

2. a trait is only adaptive is if it increases fitness (traits that are “valuble” are only considered that way bc they increase reproductive success)

3. the traits that increase fitess may change (if env changes, previous increased fitness may not be the same anymore)

how do variations in a population happen

• variations are due to genetic variations (genetic basis)

• variation of DNA sequences - individuals within a population having different inherited traits

• usually the influence of many genes (ubt it can be just one)

define

mutation

+how do they happen

+effect of mutations on fitness

+mutations and the path of evolution

• a random and heitable change in the DNA sequence

• inevitable consequence of the impeft nature of DNA replication, as well as effects of certain physical, chemical and bio agents

• muations can be helpful (increase fitness) or harmfull (lower fitness) or others have no effect

while mutations are the source of variation, they do not determine the path of evolution

why is natural selection referred to as a theory

• heritable variation leads to differental survival and reproduction

• its been tested and proven right a lot but its still a theory

define

transposable element

• a biological agent that can cause utations

• pieces of DNA hat can move from one posistion to another in the genome, sometimes inserting themselves in ways rhat affect the expression of genes

define

selection pressure

• usually an environmental pressure, that forces the populations best traits to be selected for by natural selection

define

convergent evolution

• independant evolution of comparable traits in unrelated species, such as the wings of insects, birds and bats (they all have wings but arent related)

define

generation time

• average difference in age between a parent and its offspring

• the age when an organism produces the next generation varies tremendously amond different groups

• organisms with short generation times evolve more repidly than those with longer geenration times

who challenged the religious considerations from Aristotle

• jean basptiste lamarck

• he proposed that a so-called perfectng principle whereby simple organisms evolved into more complex ones, moving yp the Scale of Nature

• …simple forms of life were believed to arise from non-living material

• his thoery was incorrect (that charcteristics during a organisms lifetime can be passed on to future generation)

• ie a giraffe extending its neck to reach higher fruits

why is Lamarcks theory wrong (3)

1. organisms do not appear through spontaneous generation

2. although muscles can grow larger through continued use, organisms cannot evolve fundemenal physiological changs during their lifetime

3. physical changes aquired during an organisms life are not passed to offspring

define vestigial structures

• useless parts of animal bone structure that remains even after the animal has evolved

define *

zoonotic disease

• diseases that jump top humans (spill over) from other animals

• at a higher risk when aniaml is more closely related to (similar zoology)

• 75% of new infection disease

• more likely b/w closely related species

• often not very harmful in the original host (resevoir) but much more in new host

define

viruses*

+obligate parisites

• protein shell with nucleic acid genome inside (DNA or RNA, single or double stranded)

• 
  

• need to infect cells to make proteins and replicate

compare the difficulty of creation for antibiotics, antifungals and antivirals*

• relative to antibiotics (bacterial infections) antifungals (fungal infections) antiviral drugs are harder to design and usually have more serious side effects

• viruses are very unique in structure compared to bacteria, which have easily identifiable structures (so drugs are easier to make…dissolve cell membrane, stop ribosomes from protein synthesis…)

• we need to identify and target processes that the viruys needs but the host cell does not

central dogma of RNA genome*

+what viruses have an RNA genome

+define reverse transcription

• retroviruses (including HIV) have an RNA

• extra step viruses take to infect the cell (through enzyme)

• very fast but also a lot of mutations (might mutation rate)

HIV lifecycle: targets immune cells

• virion fuses with host immune cell

• viral reverse transciptase reverse- transcribes viral RNA to ds DNA

• viral intergrase splices virus DNA into host DNA

• viral DNA gets transcribed, translated, and forms new virions

explain

the drug AZT*

basically how does it affect HIV life cycle and then into resistance

• nucleoside analong- shaped almost like thymine

• once RT adds AZT to the chain, DNA synthesis is blocked

• after months of AZT treatment, HIV becomes resistace (it can still synthesize)

• there is a change in the reverse transcriptase enzyme active site to make sure that the AZT cannot fit anymore (it becomes resistant)

  

• a change to two nucleotides confers to AZT resistace
  
  

how does HIV become AZT resistant*

• mutations are random mistakes

• AZT’s lowered efficacy is caused by randomized mutations, lowering efficacy

• RT makes errors in copying HIV genome (mutations) A tiny fraction of mutations improve AZT resistance

• Susceptible mother virons mostly produce daughter virons

• there is genetic and phenotypic variation in viral population

• AZT treatment: virons susceptible to treatment stop (red)

• some varients are able to reproduce in the presence of AZT = drug resistance HIV (green)

evolution of AZT resistance*

• mutations→ variation in AZT-resistance

• AZT resistance passed from “parents” to “offspring”

• nto all virons reproduce

• when AZT is present, some forms (AZT resistance) are more likely to reproduce than others (AZT- susceptible)

• viral populations changes over time (b/c resistance strand will survive)

how does evolution by natural selection

• variation + nonrandom survival

“mutation proposes, selection disposes” *

• new genetic variants (mutations) are constantly occuring, regardless of the environment

• the environment (in this case presence vs absence of AZT) affect which variants become more common, not which variants occur

• environment determines how abundant a strand/genome would be over another

HIV’s high mutation rate also makes vaccine development challenging*

• mutations in HIV’s other genes change the outer structure of the virus

• this lets HIV hide from out immune system

• hard to design vaccine to account for all potential varients

• there is not universal HIV vaccine (yet!)

consider these questions…cycle 1*

difference between belief system and scientific theory*

belif system

• a set of principles or belifs which togeth\er form the basis of a religion, philosophy, or moral code

• belif- conviction or acceptance that certain things are true or real, faith

• not intended to be tested or rely on evidence

scientific theory

• coherent set of testable hypothesis that try to explain facts about the natural world

• must be tesable and falsifiable. if falsified, change the theory

• to be a scientific theory, it must should be able to be tested

to be scientifc, an idea (theory must be most testable and falsifiable*

• some possibel observation or experiemental finding could prove the theory (or hypothesis) wrong

• “AZT-resistance forms of HIV will increase in frequency whenever a patient is takign AZT. These forms will NOT increase in frequency if the patient is not taking AZT” (easiy to test)

• “positive thinking can cure cancer, if you try hard enough” (hard to test)

what is the theory of evolution* (6)

descent with modification frrom a common ancestor

1. evolution happens (allele frequencies (and phenotyes) in a population change from one generation to next

2. all life is related through common ancestry

3. speciation: lineages diverge into daughter lineages

4. evolution is not transformational, it is variational. individuals do not evolve within a lifetime; populations evolve from one generation to the next

5. gradualism and transitional forms (intermediate): takes many generations to produce large changes; some transitional forms may be found in the fossil record

6. selection generates adaptation, and explains much evolutionary change (but not all)
   
   

darwin vs lamarck views on evolution 9the names of their view and how it works)*

lamarck believed that individuals could change to theoir circumstances (ie giraffes extending their neck) transformational view

• over lifetime, change phenotype to be better suited to environment

Darwin supports variational view

• those that mutated have a higher chance of surviving and propagating

common misconceptions about evolutionary theory*

• mutatins are directed towards the needs of teh organism (mutations are random)

• humans decended from chimpanzees (descended does not mean related to)

• humans are more highly evolved than plants…some species are more highly evolved than others( structurally might be more complex but not necessarily highly evolved)

• evolution and selection are the same thing

• selection mades organisms perfectly suited to their environment

• all evolution is due to selection (theres also gene flow…)

explain cell cycle

G1 - growth 1

• period of cell growth before DNA replicates

• cell can function in G1 9and its also preparing for S phase)

G0

• cell cycle arrest

• can exit or enter this cycle

• some places in the body have vert fast replication (ie. skin)

• others dont need to replicate (ie neurons)

S (synthesis)

• period when DNA replicates and chromosomal proteins are duplicated

• lots of E required

G2

• period after DNA replicates; cell prepares for division

Mitosis (meiosis)

• Prophase

• Metaphase

• Anaphase

• Telophase

Cytokinesis

***G1,G2 are preparatory phases

what happens within embryos in reference to division/differentiation

• replication is not the only thing that happens but the cell DIFFERENTIATE

• as cell divides, cell will specialize into difference types of cells

• Happens in G1…where cell makes important decisions

• early embryonic stage…differentiation doesnt really happen (cell just wants to divide as much as possible)

explain

cell turnover rate (for egg and sperm)

+other cells

• the cell turnover rate for eggs is lifetime compared to sperm cells which is about 2 months

• since sperm cells reproduce a lot more than eggs, they are more prone to mutations

• but as the woman gets older, the replication process gets sloppy and she has a higher chance of developing mutations

• for other cells, some regen very fast and some never have to regen

why do cells divide? Why not just grow larger?

• volume of the cell is contatnly increasing ..surface area isnt as fast (cell division restores a larger membrane area relative to the amount of cytoplasm)

• so cells dvided to increase the surface are to volume ratio

• required for growth and development, tissue repair and regeneration, and productio of specialized cells and gametes

• high SA:V ratio = efficient exchange across membrane

• low SA:V ratio= exchange cannot keep up with cellular demand

where are the checkpoints for cellular reproduction?

G1/S

• right at the end of G1, right before S

• cell makes sure everything is perfect BEFORE the cell replicates (most important)

• in G1, all the cell is doing is growing in size…DNA hasnt replicated yet

G2/M

• right at the end of G2, before M

• molescules come together

• repair enzyme and check genome

• “are we ready for mitosis”

Mitotic spindle

• during metaphase

• makes sure the chromatids are pulled apart properly

• if they arent, this causes disjunction which can lead to aneuploidy

define

aneuploidy

less/more chromosomes than normal

explain

positive regulation: cyclins and CDKs

• positive regulation is like a green light for cellular reproduction

CDK- cyclin dependent kinase

CAK - CDK activating kinase

• unactive cyclin is close to CDK active site…still not active

• CAK, which is a phosphate donating enzyme, allows cyclin to attach to CDK and activates the complex (via phosphorylation)

• cyclin-CDK complex is phosphorylated and the activated complex then phosphorylates target protein

• target protein now has phosphate…changes conformation into active form

• this allows cell to more into the next stage of cell cycle

explain

negative regulation: p53 and p21

p53 acts like the guardian of the genome

when there is no DNA damage = cell cycle continues

when there IS DNA damage

• p53 (guard) activates p21 (army)

• cell is put into temporary cell cycle arrest

• If repair is successful, cell cycle continues

• if repair isnt successful, damage persists and cell goes to apoptosis

define apoptosis

• programmed cell death

explain

p53 inhibiting cycle-CDK by targeting p21 production

• p53 detects DNA damage and increases p21 production by binding to the p21 promoter

• p53 acts as a transcription factor to activate the p21 gene to produce more p21

• p21 is produces and looks for the active cyclin-CDK complex

• p21 is a cyclin-CDK inhibitor

• inactivated by the binding of p21, the cyclin-cdk complex cannot phosphorylate proteins involved in cell cycling