Cell final review ALL

Define chromatin

A single package of DNA (half of a chromosome) and protein

Chroma (color) PLUS protein = chromatin

define heterochromatin

Chromatin that is highly condensed and contains silenced genes or very few genes

• different types depending of location

Define euchromatin

Less condensed chromatin that can be packed into heterochromatin

• genes close to heterochromatin (even if its suppose to be euchromatin) are affected because condensation spreads

Define polytene chromosome

Chromosomes that aid in understanding chromatin organization

• histone variants and non-histone proteins makes for differential regulation of gene expression and varying roles in a cell

• differences in condensation levels within a chromosome

Define condensins

Large proteins that act like combs that DNA can twist around

• located at the base of loops near scaffold

• when gene is going to be transcribed, the area decondenses, unwinds, and transcibes

Define nucleosomes

The basic unit of chromatin structure

• Made up of packed histones

each nucleosome has ~200 bp of DNA wrapped around it & contains 2 of each four histone subunits.

nucleosome is the actual circle with the DNA (histone + DNA)

Define histones

Small proteins that bind DNA via 142 hydrogen bonds

• contain a lot of arginine and lysine (positively charged)

  • binds to negative DNA

Make up the first level of organization and are packed into nucleosomes.

Has 4 subunits and together make an octamer

Define ploidy

the number of sets of chromosomes in a cell, or in the cells of an organism.

Define conserved synteny

Parts of mammal’s genome that is contains the exact same genes in the exact same order (in humans found in other mammals)

Define fractal globule

Chromosome with a physical structure that allows it to change shape (unfold/fold & densely/loosely packed)

• can fold and unfold as necessary (solenoid model)

Label the 3 parts of the chromosome

1. Centromere = allows one copy of each duplicate to be pulled into each daughter cell

2. p arm = short arm

3. q arm = long arm

Name each type of chromosome based on the location of the centromere

Metacentric = centromere found straight in the middle of the chromatin

Submetacentric = centromere found slightly off center (different arm lengths)

Acrocentric = centromere found on the edge of the chromatin (very small p and large q)

• ex: chromosomes 13, 14, 15, 21, & 22

What is important about a centromere

Centromere = allows one copy of each duplicate to be pulled into each daughter cell 

• Kinetochore (little protein) at the centromere forms and attaches both centromeres to the mitotic spindles 

Describe transposons & its percentage

~40%

• DNA that was inserted over long periods of time

  • usually are unused, but sometimes can insert themselves in new locations that cause a mutation or new function

• “mobile genetic elements”

• parasitic sequences that can disrupt function or alter gene regulation “jumping genes”

  • not always bad

Describe introns and their percentage

~20%

• Don’t code for proteins

Describe exons and their percentage

~1-2%

• code for proteins

Describe genes and their percentage in the genome

~20%

• Code for something, have a process in the protein function/development

What are the 3 major components necessary for chromosomal function (list)

1. replication origins = where DNA dupication begins

   • there are many and all simultaneously begin replication

2. Centromere = allows one copy of each duplicate to be pulled into each daughter cell

   • Kinetochore (little protein) at the centromere forms and attaches both centromeres to the mitotic spindles

3. Telomeres = Repeated sequences forming the ends of a chromosome

   • protect it from being eaten by DNA repair genes and replication

What are the cell cycle phases & chromosomal state in each

Interphase = interphase chromosomes are replicated and are very loose

• DNA easy to access

• 1 chromatid only

Mitotic phases (M phase) = mitotic chromosomes are now highly condensed so they can be separated/distributed into 2 daughter nuclei

How do chromosomes change states (compaction level) between cell cycle states and proteins involved

Condenses are large proteins that further condense the fiber loops

• when a gene needs to be expressed, it unwinds

histones are the octamer proteins that begin the condensing process

What is a nucleosome? It’s function, proteins involved in packaging DNA, and structure

Nucleosomes = the basic unit of chromatin structure

• DNA wound around a histone core (THE BEAD)

  • 200bp of DNA wrapped around it

• contains 2 of each histone subunit (histone octomer)

  • held together via 142 hydrogen bonds

• makes DNA 1/3 of it’s original length

What are the type nucleosome packaging models?

Space-filling model

• nucleosome made up 4 histone types (proteins)

• four histone types bind to DNA with hydrogen bonds

• histones have a lot of arginine and lysine (positive charge) that is attracted to DNA’s negative charge

Zig zag model

• Nucleosomes structured into a chromatin fiber

Solenoid model

• chromosome folds and unfolds into densely or loosely packed chromatin making a fractal globule

  • Has a physical structure that allows it to change shape

State the role of histones and chromatin forms in cells, including structure and function

Histones = first level of organization

• packs into nucleosomes

Chromatin

• Fiber with a 30nm diameter

• Can form chromatin loops that can range between 50k-200k

chromatin loops

• Can decondence and condence with condensin proteins (when unwound, the region can be transcribed/active transcription)

Define and explain chromatin/chromosome territories within a cell nucleus

Interphase chromosomes occupy discrete territories in the cell nucleus; that is, they are not extensively intertwined.

• chromatin moves around in the nucleus (territories can change depending on the level of expression required of the gene)

  • gene rich regions tend to move centrally in the nucleus

Describe the packing and organization of DNA in chromosomes (include timing during cell cycle & proteins involved)

DNA

Histone

nucleosomes

30nm fiber

loop domains

chromatin fiber

Mitotic chromosome

What is the process of DNA replication (eukaryotic)

Origin of replication

DNA replication process: (on loose DNA) 

1. Initiator proteins (ORC) bind to origin 

   • The origin is usually a sequence rich in ATs 

   • Chromatin structure/transcriptional activity may define origins 

2. DNA/protein binding at origin calls over the helicase 

   • Helicase unwinds the DNA when it is phosphorylated 

3. Both the ORC and helicase are phosphorylated  

   • ORC is inactive 

   • Helicase is active (begins unwinding) 

4. Primase comes and makes the RNA primer 

   • DNA polymerase alpha 

5. DNA polymerase ε begins transcribing the leading strand & DNA polymerase δ makes the lagging strand 

6. Nucleosome/histone reassembly (semi-conservative) 

   • Increased mRNA histone transcription & decreased mRNA destruction 

   • Preparing for M phase (which is highly condensed) & double amount of DNA 

List the cellular mechanisms that help avoid error generation during DNA synthesis

ORC being highly regulated 

• Phosphorylation controlling activation/inactivation 

Mismatch repair genes are signaled by “nicks” in DNA to come and fix it 

• Strand directed mismatch repair 

• Muts comes to error, determines which is the daughter/parent strand, cuts out error, DNA polymerase comes and synthesis 

DNA polymerase selectivity/proofreading

Cell cycle checkpoints

DNA repair pathways

How do the phases of the cell cycle relate to DNA replication

G1 phase = ORC sets up (everything is brought) 

• Phosphorylate helicase/ORC to begin replication 

S phase = replication only occurs during S phase (in interphase) 

• Everything gets replicated 

G2 phase = repairs any DNA mistakes made during S phase 

M phase (mitosis) = separation/daughter cell forms

Define telomeres

repeated ends that are a “counting mechanism” to avoid unwanted cell proliferation 

• Repeated sequence (TTAGGG) at ends 

• When ends get too short (can no longer keep up with chromosome duplication) the cell stops dividing and dies 

• In cancers, there can be issues with telomerase 

Disease with dysfunctional replication

Trinucleotide (triplet) repeats = replication errors 

• Di/trinucleotides located in repetitive sequences in an unstable area leading to slippage and expansion during replication 

  Lagging strand will make a bubble -> to expanded sequence 

  BER can keep this from happening 

• Ex: Huntington’s, FXS, and myotonic dystrophy 

What enzyme makes/assembles telomeres

Telomerase = replicate the ends of chromosomes (reverse transcriptase) 

• 3’ end always longer, therefore tucks into t-loop (double DNA strand) 

What is one disease that is due too telomerase issues

Dyskeratosis congenita = abnormally short telomeres 

Missing nails, alopecia, and abnormal skin pigmentation 

Define germ cell

transmit genetic info from parent to offspring 

• Contain heritable information, so it WILL affect the offspring  

• Ex: eggs/sperm  

Define somatic cell

form the body 

• Mutations will only affect the body and NOT the offspring 

Define mutation

permanent change in DNA  

• Can be good or bad 

• Mutation rate = rate at which observable changes occur in DNA sequence  

  ~1 nucleotide change per 1 billion nucleotides 

• Advantage mutation = ability to proliferate extensively and spread to unknown foreign areas of host 

  Survive at expense of host 

Define replication fork

where helicase unwinds/opens strands and replication moves along the parental DNA double strands  

• Active region of replication 

• RNA primer required  

• Produces 2 asymmetric strands (leading/lagging strands) 

  Leading strand synthesis precedes lagging strand 

• ORC primarily found in AT rich sites and euchromatin regions 

Define replication bubble

a region of the DNA double helix that has unwound and opened to allow for DNA replication

• both of the replication fork areas (opened)

Define DNA polymerase

an enzyme that synthesizes DNA molecules using existing DNA as a template

Define the leading strand

Strand that’s continuously synthesized by DNA  

Define the lagging strand

Strand that is synthesized discontinuously in fragments  

• The fragments are known as Okazaki fragments – leaked together with DNA polymerase 

Define ligase

seals DNA strands (or DNA areas) together

Define primase

adds RNA primer 

• Acts as guide  

• Part of replication machinery 

Define helicase

breaks strands apart 

• Breaks hydrogen bonds 

  Usually start at AT sites because they are “easier” to break 

• Part of replication machinery 

Define topoisomerase

keeps DNA double strand from becoming tangled as it unwinds 

• Part of replication machinery 

Define Okazaki fragment

short, newly synthesized segments of DNA on the lagging strand during DNA replication

Define pre-replicative complex

a protein complex that forms at the origin of replication, a specific DNA sequence, in eukaryotic cells

• different from the ORC

Define telomerase

an enzyme that adds nucleotides to telomeres

• added to the ends of DNA - to maintain the length of telomeres

What are the functions of DNA polymerase

Synthesize new DNA strands, ensuring accurate replication and the maintenance of genetic information 

SERVES AS A PROOFREADER & ERROR CORRECTOR 

• Finishes Okazaki fragments & leading strands 

• provides exonucleolytic activity to remove mismatched bases 

• drives DNA repair with the energy of phosphodiester bond formation 

Family A 

Pol y = replicates and repairs mitochondrial DNA 

Family B 

Pol α = starts RNA primer synthesis (primase) 

Pol δ = makes lagging strand 

Pol ε = makes leading strand 

Family X 

Pol β = DNA repair 

Pol λ & µ = NHEJ repair 

Family Y 

Pol n, l, & k = Trans lesion synthesis (push through errors) 

Identify the leading/lagging strands

In what direction is DNA synthesized

DNA is synthesized 5’ to 3’

What is an aneuploidy

loss/gain chr.

ex: Down syndrome, Turner’s, & Klinefelter’s

What is a isochrome formation

two of the same arm – q or p

• one arm is lost and the other is copied (replaces the missing arm)

  Ex: Angelman disease

What is Cri-du chat disease

Deletion on short arm of chromosome 5 (arm p) 

• Deletion of 5p 

• Profound retardation and cat like speaking (issues with larynx) 

What is down syndrome

Autosomal aneuploidy (trisomy) 

• 3 chromosome 21 

* Isochrome of chromosome 21 (2 q arms) can have similar phenotype to DS 

What is Klinefelter’s

WSex chromosome aneuploidy (trisomy) 

• XXY 

• Mixture of female/male characteristics (usually sterile) 

What is Turner’s syndrome

Sex chromosome aneuploidy (monosomy) 

• XO 

• Short stature, underdeveloped sexual characteristics (usually sterile) 

What is CML (Chronic Myelogenous Leukemia)

Translocation between chromosome 9 & 22  

• The ends of both chromosomes q arms are translocated 

• Bone marrow disease characterized by increased WBC line proliferation 

What is Angelman disease

Isochrome of chromosome 15 (two maternal q arms) 

• The paternal chromosome is normal; the maternal chromosome is the one with the isochrome characteristics (2 chromosome 15 q arms) 

Define antiparallel

the two strands of the double helix run in opposite directions

Define base

A nitrogen-containing rings  

• Purine or pyrimidine 

• Chemically/physically distinguishable 

• CuT = pyrimidine 

• Au:Gold = purines 

Define base pair

• Purines CANNOT bind to other purines because of chemical structure 

• Keto group of one base binds to amino group of another 

Define complementarity

one strand complements the other 

• Necessary because of base pairing requirements (hydrogen bond formation)

Define double helix

a pair of antiparallel helices intertwined about a common axis, especially that in the structure of the DNA molecule.

Define template

A pair of parallel helices intertwined about a common axis, especially that in the structure of the DNA molecule.

• A DNA mold that codes for other DNA or proteins

Define intron

part of a sequence that is not used to make a protein structure 

• “unused” - but does have some unknown function 

Define exon

part of a sequence that is used/transcribed into mRNA or eventually proteins 

• Spliced together to form a functional gene 

What type of bond exists between bases/across DNA

Hydrogen bonds

• contribute to double helix stability

What type of bonds are between sugar and phosphate in DNA backbone?

Covalent bonds

• strong chemical bond with a sharing of electron pairs with a balance of attractive and repulsive forces

How many hydrogens bonds are between C-G and A-T

3 and 2

What makes up a nucleotide

nitrogenous base, five carbon sugar, and phosphate group 

• Sugar and phosphate form DNA back bone with covalent bonds 

Where are phosphodiester bonds found

between the sugar and phosphate group in backbone

• nucleotides are joined by the PO4 of one nucleotide attaching to the 3’ carbon of the next nucleotide to form a polynucleotide 

Identify the boxes and the bonds

See the image

What is the function of DNA in the overall physiology of the body

Purpose of DNA = to archive information 

• Not functional without it forming RNA 

• Is the blueprint for everything else  

  Protected in the nuclear membrane so it doesn’t get transported out or damaged 

• Only 1% of human genome is protein coding  

What are universal features of ALL cells

The universal features of ALL cells:  

• DNA is the hereditary storage of information  

• Cells replicate through template polymerization (using DNA to undergo synthesis) 

• Use RNA as intermediate via transcription (proteins aren’t always end product) 

• Use proteins as enzyme catalysts to form new DNA 

• Use tRNA to translate RNA into protein 

• Proteins encoded by specific genes 

• Free energy (ATP) required for many cell processes) 

• Have plasma membrane  

• Can have as little as 300 genes  

Define DNA

Double stranded long polymer chain composed of sequences of four monomers (hereditary information storage) double helix with bases attached via hydrogen bonds (hydrogen bonds across nucleotides/bases) 

Define RNA

single stranded polymer that is flexible and can fold back on itself & can complementarily bind to other molecules/sequences 

Define DNA replication

Copying (template polymerization) single strand of DNA to form another DNA strand (hydrogen bonds between bases of strands are broken) 

Define templated polymerization

Using 1 copy of a DNA/RNA strand to make a new complimentary DNA/RNA strand  

Define transcription

RNA synthesis. Making mRNA from a DNA strand (first step of protein synthesis) 

Define translation

Protein synthesis. Making a protein from a mRNA strand

Define Codon

three nucleotides that are transcribed into an amino acid by transcribing the mRNA sequence 

Define nucleotide

a sugar with phosphate group attached to a base (a single monomer in a single strand of DNA) 

Define genetic redundancy

several codons can make the same amino acid (helps avoid translating point mutations) 

Define a gene

a fundamental unit of inheritance, a segment of DNA or RNA that carries the code for a specific protein or RNA molecule

What are 3 differences between DNA and RNA

DNA	RNA
Is fixed (all cells contain it & will always be there)  Archive of information  Sugar made of deoxyribose	Is disposable, meaning it won’t always be present within cells  Mass produced  Sugar made of ribose

What is an autocatalytic

protein with self-replicating feedback loop 

• Pathway makes protein and then the protein goes back and promotes more protein synthesis (or a stop) 

What is a lysozyme

an enzyme that breaks apart polysaccharide chains (degrades other compounds) 

• Stored in the lysosome, protected by the membrane, so it doesn’t affect other processes within the cell 

How can proteins direct cellular processing?

By acting as a catalysts/enzyme

Ex: Lysozymes

What are some lysosomal storage diseases

Gaucher disease, Tay-sachs, metachromatic leukodystrophy, hurler syndromes

What is Gaucher disease

Deficiency of beta-glucosidase => glycosphingolipids accumulate => enlarged liver/spleen (Gaucher cells appear in bone marrow)

RETICULOENDOTHELIA SYSTEM (RES) DISEASE (phagocytes in immune system)  

What is Tay-Sachs

Deficiency of hexosaminidase => accumulation of gangliosides in brain (break down cells) => mental retardation (hearing/vision loss)

CNS DISEASE

Common in ASHKENAZIC JEWS 

What is Metachromatic leukodystrophy

Deficiency of arylsulfatase A => buildup of glycosphingolipid in white matter of brain and cord => damages neurons => hyper flexed muscles

CNS DISEASE 

What is Hurler syndromes

Deficiency in alpha iduronidase => lack of collagen => lack of structural formation

Can’t break down Mucopolysaccharidoses because lack of lysozymes (build up)

SKELETAL & COLLAGEN DISEASE 

What is the basic structures of mammalian eukaryotic cells

More elaborate structures (organelles, compartments, membranes) 

• Nucleolus, nuclear envelope, mitochondria, nucleus, Golgi apparatus, microtubules 

Define regulatory proteins

Proteins that regulate other proteins’ production/synthesis by binding to regulatory sequences  

Coding region -> mRNA -> protein -> binds to regulatory sequence -> affects protein production 

Define genome

all of the genetic makeup of an organism (all of the DNA) 

• The entire DNA sequence of an organism 

Define prokaryote

singled cell organism that can live independently and have no organelles or nucleus (free floating DNA) 

Define eukaryote

complex cell that contains organelles, cytoskeleton, and has the ability to phagocytose things

Gene transcription

process of copying a segment of DNA into RNA for the purpose of gene expression.

What are key differences between prokaryotes and eukaryotes

Prokaryotes	Eukaryotes
Live independently   No nuclear compartment  No nucleus, mitochondria  Cell wall outside plasma membrane   Can have a flagella	More elaborate structures (compartments)  DNA in nucleus  Complex cytoskeleton (provide strength, shape, and movement)  Ability to phagocytose (engulf other cells or organisms)