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Chapter 12: The Nucleus

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10/15/15
Intro
all cells in multi-cell organisms contain the same cpmplement of genes
express their genetic information selectively
gene expression controlled by regulatory machinery in cell nucleus
transcriptional control
most important and most common
gene activation, transcription, splicing, nuclear,
translational control
sRNA, mRNA
post-translational control
protein modifications, degradation, inhibitors
after proteins have been made
Control of Gene Expression in BActeria
bacterial cells selectively express genes to use available resources effectively
presence of lactose in medium induces synthesis
The BActerial Operon
genomes are a lot smaller, take all genes necessary and stick them in a group together called
an operon
has 1 promoter region (P block)
operator region: site between promoter and genes where some proteins can bind
if binds creates a physical barrier and keeps the rest of the genes from being transcribed
this is a represser
The lac Operon
inducible operon
turned on when lactose is present
lacZ, lacY, and lacA
operator is where protein changes gene expression, under normal expression block at the
operator
RNA polymerase cant get through
exposed and falls off the operator
make 3 enxymes that are necessary
transcribed as 1 long mRNA and let the ribosome sort it out
Catabolite Repression of the lac Operon
gene that cods for repressor protein is anywhere else int he genome
lactose present, bacteria exposed, operator free and repressor protein falls off
glucose effect is an example of positive control
cyclic AMP (cAMP) forms when glucose are low
cAMP acts by binding to a receptor protein (CRP)
binding of CRP-cAMP to the lac control region changed the conformation of DNA thus allowing
RNA polymerase to transcribe the lac operon with high efficiency
The Trp Operon
repressible operon, turned off in presence of trp
not getting enough, turn genes on (5 structural genes) and make long RNA
Riboswitches
change DNA expression, usually at translational level
block last bit of transcription or first part of translation
undergo conformational switch
number og bacterual mRNAs can bind to a small metabolite

i.

like sugars or amino acids, other products from diet and help control gene expression
tend to be legacies of an RNA world, can respond to cofactors
Control of expression in Eukaryotes
controlled by proteins binding to DNA
start from nucleus and work in
nucleus usually has chromosomes,
nucleoli, for rRNA synthesis
i.
christmas tree patterns
e. nucleoplasms, as the fluid where solutes are dissolved
f. nuclear matrix, which is the protein-containing fibrillar network
9. Nuclear Envelope
a. divides the nucleus from its cytoplasm
b. conists of two membranes separated by nuclear space
c. pores in the membrane, pinch together at certain regions
d. proteins make basket like things to hold the pore open
i.
controls what goes in and out of the nucleus
e. transmember protein connects to stuff outside the nucleus and for through both layers of the
nucleus
10. Nuclear lamina
a. supports nuclear envelope and composed of lamins
b. controlled by addition of phosphate group conformational changes
c. progeria is not inherited from parents, dominant mutations, new mutations
i.
dont live past teens and dont live to have children of their own
d. lamin B results in lack of control of muscles and paralysis, give membrane structure and support
i.
slow aging of cells in progeria? also reduce wrinkles
11. Something
12. Importing Proteins into the nucleus
a. proteins synthesized in the cytoplasm are targeted by the nuclear localization signal (NLS)
having basic residues
b. heat shock protein helps refold protein after the hydrophobic area is exposed
c. NLS stretch binds to an NLS receptor (importin)
d. allows to pass through nuclear pore complex
13. Chromosomes and Chromatin
a. packaging the genome
i.
chromosomes consist of chromatin fibers to help compact it composed of DNA and proteins
ii.
histone: highly basic amino acids like lysine
b. Nucleosomes:
i.
see nucleosomes forming like beads on a string
ii.
histones is an octomer of 4 subunits, H2A, H2B, H3 and H4
14. Nucleosome Structure and Function
a. DNA wraps around the outside of the histones and wrap like thread on a stool
b. get tails hanging off of the histone proteins and can be modified which controls whether it is
stuck close or not and whether RNA
c. DNA stuck more closely in certain places so tissues dont make fingernail structures
15. Higher Level of Chromatin Structure
a. wrap up on themselves and form more compacted structures
b. controlled komstly by H1 (used as linker)
c. zig zag: trans OR solenoid: cis
i.
get same amount of folding but different way
d. loops: permanently silent genes, inactive X chromosomes, etc
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e. reduced 6 feet of DNA to about 10 inches


f. using H1 proteins gets it down to just under 2 inches
g. ultimate chromosome compaction is 10,000 - 1 and DNA is less than .2 mm and can fit in 10
mm nucleus side to side
16. Heterochromatin and Euchromatin
a. Euchromatin:
b. heterochromatin: dense phase, occurs during interphase,
c. constitutive heterochromatin: some remain condensed all the time
i.
usually around centromeres and telomeres
d. faculatative heterochromatin: we turn off 1 copy of X chromosome and shut off permanently,
protection against double the hormonal load
i.
some cells express 1, other cells express the other, random throughout the entire body
ii.
inactivated during certain phases of the organism
1. calico cat: black is one X and orange is the other X
2. clone her it wouldnt look like her and patches dont go in the same pattern
e. 5 genes involved and not sure exaclty what they do,
i.
XIST coats X chromosome and keeps it compacted
17. Histone Code and Formation of Heterochromatin
a. stretched of amino acid sequences that have tails, the AA are modified by phosphorylation,
addition of methyl or ethyl and other stuff.
i.
modifications influence how tightly the DNA holds to the histone
ii.
some can recruit other proteins
iii.
pack more tigthyl: positive charge but sometie randon
18. Proteins bind selectively to modified H3 of H4
a. acetlyate the same version and activating, methyl is usually silencing
b. order of mods and which present is complex and why we call it the histing code, have to look as
what AA and where its located
c. obese permanantely change genetics, differs between obese and not obese so harder for them
to lose weight
19. Histone Modifications & Transcriptioonal Activity
a. acetylation is generally activating
b. monomethylation is activating on certain positions but if add 2 methyls it is repressing and 3 is
either, depends on other amino acids near it
c. ubiquitination: targets proteins for degredation, usually only 1 group of ubiquitin is added and
the the protein degrades
20. transcriptional activity and hitone acetylaytion
a. binds to tails and bind it more dense heterochromatin
21. Histone Mods
a. associated histones and DNA more closely
b. carbnonyll repels negative DNA
c. add methyls and further compacts
22. Structure of a Mitotic Chromosome
a. downs: extra chromosome of 21, any other chromosomes seem to be fatal
b. karyotype: preparation of homologous pairs ordered according to size
23. Telomeres
a. get a little hsorter each time the cell divides, when it gets too short supposed to stop but
sometimes cells dint
b. TTAGGG
c. like an aglet on a showlace

d. added on to chromosoes using telomerase, ove created and run out of telomeres the cell is
supposed to die
e. investigate life span, if could extend these you could regenerate tissues as you get over
f. cancers and tumors turn this enzyme off
i.
live longer? but have higher possibility of cancer
24. nd-Replication Causes Telomeres Shortening
a. each time you cant cover last little end, cant remove last little peice of RNA and get a gap and
get shorter as they replicate
b. protect from degredation
c. Hay-flick limit?: how long can you get them to divide
i.
dont have enough cells left that can still divide
25. Telomerase Complex
a. telomerase associated with multiple other proteins
b. take cells grow in petri dish and treat with green tea extract, can turn on expression of tert which
is the active part of the telomerase
c. none of the rest was turned on, like TERC, hep 1, and other stuff
d. HSP90, Ub, PO4 3-, tc
26. Telomeres maintained differently in different cell lineages
a. 90% cancers have active telomeres

Essay: transcription/translation and lac operon of trp operon

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