Genomic Regulation, Theisen

Question 1

Microarray

Answer 1

can get all known genes in virus (cancer) , probes for RNA

up and down regulation of genes in various tumors

classify families based on enzyme function, tissue expression, and type of cancer,

ex: just for leukemia

Question 2

tRNA

Answer 2

transfer AA to ribosome for protein synthesis

Question 3

mRNA

Answer 3

codes for proteins

contains the base pairs for AA

Question 4

rRNA

Answer 4

structural RNA

combines with proteins to form ribosomes

Question 5

snRNA (small nuclear)

Answer 5

part of spliceosomes

involved in splicing of precursor mRNA

Question 6

scRNA (small cytoplasmic)

Answer 6

involved in protein processing and secretion

Question 7

RNaseP (ribonuclease P)

Answer 7

a catalytic RNA (ribozyme)

involved in cleavage and removal of extra RNA sequence

Question 8

siRNA (short interfering)

Answer 8

derived from transposons
complementary to mRNA’s
inhibits translation and enhances mRNA degradation

Question 9

miRNA (micro)

Answer 9

involved in post transcriptional regulation of gene expression
associated with diseases

ex: iRNA

Question 10

Alternative Splicing

Answer 10

exons may be included/joined together in final mRNA

rearrange exons, can skip some and glue together others to make sequences of RNA into mRNA

Question 11

RNA interference

Answer 11

small regions in the genome, some are genes with a promoter and codes for RNA

these are not translated but are complementary to strand that will make an enzyme

Question 12

DNA transposon

Answer 12

elements in our own genome

long repetitive sequences

Question 13

LTR retrotransposons

Answer 13

acts more like a virus/retrovirus

genome is transcribed into RNA and then reverse translated into DNA (our DNA)

Question 14

Non-LTR retrotransposons

Answer 14

control mechanisms
do not have long terminal repeats
take on the likeness of an integrated RNA

Question 15

Retrotransposons

Answer 15

Type 1 of transposons
proviral DNA
mobile DNA sequence, change position in the genome

Question 16

Euchromatin

Answer 16

less condensed
constantly available
this genes are constantly on
available for mRNA processing and transcription events

ex: GAPDH, ATCase, HGPRT

Question 17

Heterochromatin

Answer 17

very condensed chromatin
contain more viral transposons
have less used information

Question 18

Histone acetylation

Answer 18

turns on a gene
removes part of the histone to remove charge and make less attraction between the histone and the DNA

allows the DNA to be loosely attached which is better for transcription

DNA is negatively charged and histones have Lys and Arg (positive charges)

Question 19

Histone methylation

Answer 19

a methyl group is placed on a histone
creates a physical barrier to loosen attraction of histone and DNA

creates an increase in transcription

Question 20

Histone/Nucleosome info

Answer 20

there are 8 histone proteins

each nucleosome has 4 proteins in it

Question 21

DNA methylation

Answer 21

methyl group opens up the DNA by creating physical interference

usually silences transcription
can be inheritable (cancer)

accumulation of methyl groups is passed down

Question 22

Helicase

Answer 22

protein responsible for unwinding of the DNA helix during replication

needed to complete the fork

breaks apart base pairs and forces them to stay separated

Question 23

Topoisomerase

Answer 23

a reversible enzyme

breaks phosphodiester bonds to change superhelicity caused by the unwinding of DNA

relieves supercoiling due to helicase action

Question 24

Telomeres

Answer 24

found at the end of chromosome strands for protection

shorten over time due to aging

Question 25

Telomerase

Answer 25

brings its own primer prevents shortening of the strand by adding DNA pieces to the ends of strand after cell division in tumors, telomerase is overactive, repairs the telomeres and allows cancer cells to replicate

Question 26

Intercalating agents

Answer 26

high affinity for DNA and cause replications and fidelity when attached ex: thalidomide, ethidium bromide

Question 27

Direct Repair (enzymatic repair)

Answer 27

Damage repaired: - pyrimidine dimers - O6 methylguanine Enzymes/mechanism/disorder: - DNA photolyase cuts pyrimidine dimers using visible light - methylguanine methyltransferase removes methyl group

Question 28

Base excision repair (BER)

Answer 28

Damage repaired: - single base mistakes - non-distorting alterations (depurination) Enzymes/mechanism/disorder: - glycolases remove unmatched base (cleave glycosyl bond - DNA glycolase, AP endonuclease - AP lyase - DNA polymerase, DNA ligase

Question 29

Nucleotide excision repair (NER)

Answer 29

Damage repaired: chemical adducts that distort DNA - pyrimidine dimers, BPDE-guanine adducts (benzopyrene) - cisplatin adducts Enzymes/mechanism/disorder: - NER complex unwinds double strand, phophodiester bond broken, makes a nick, removes damaged nucleotides - DNA polymerase fills in missing gap and nick is sealed by DNA ligase Disease: Xeroderma Pigmentosum

Question 30

Mismatch excision repair (MER)

Answer 30

Damage repaired: -mismatched base in daughter strand Enzymes/mechanism/disorder: -MER complex, helices/endonuclease, DNA polymerase DNA ligase -endonuclease cuts daughter strand -helicase/endonuclease removes mismatch segment polymerase fills in and ligase seals Disease: Hereditary nonpolyposis colorectal cancer

Question 31

Recombination Repair - nonhomologous (NHEJ) - homologous

Answer 31

Damage repaired: - double stranded breaks - interstrand cross linking Enzymes/mechanism/disorder: -exonuclease, DNA polymerase, MER system nonhomologous: blunt ends brought together with nuclease and then ligase homologous: sharing of overhang 3' twists with bottom strand through DNA polymerase Disease: BRCA1, BRCA2 = breast cancer

Question 32

Transition coupled repair (TCR)

Answer 32

Damage repaired: -stalled RNA polymerase during transcription Enzymes/mechanism/disorder: -recruits other repair proteins Disease: Cockayne Syndrome

Question 33

Translesion Synthesis (bypass synthesis)

Answer 33

Damage repaired: -unrepaired thymine dimers or apurini AP sites Enzymes/mechanism/disorder: -DNA polymerases (reduced fidelity polymerases)

Question 34

Spontaneous DNA Damage

Answer 34

depurination (loss of purine bases) deamination - changes of bases, C to U UV radiation = non-ionizing damage, causes thymine dimers to form through covalent interaction formation of thymine and Tyr linkages are an example of non-ionizing damage

Question 35

CPG Islands/CPG Sites

Answer 35

adjacent cytosine-phosphate-guanine methylation of these islands to the cytosine is problematic this causes silencing of genes (Cancer/DNA repair genes)

Question 36

Xeroderma pigmentosum

Answer 36

inherited proteins in NER complex affected UV from sunlight causes cyclobutane thymine dimers to form in DNA these dimers get repaired in normal, healthy NER complexes

Question 37

Hereditary non-polyposis colorectal cancer

Answer 37

inherited mutations in one of alleles of genes in MER complex (MSH2 or MLH1) leads to an increased susceptibility to this cancer acquired mutation of second allele (good copy) leads to MER nonfunction and thus tumor development

Question 38

BRCA1/BRCA 2: Breast Cancer

Answer 38

these are breast cancer susceptibility genes also tumor suppressor genes mutations cause a 5x increase in developing breast/ovarian cancer men have some risks too

Question 39

Cockayne's Syndrome

Answer 39

autosomal recessive mutant ERCC6 and ERCC8 genes defect in transcription coupled repair (TCR) sx: growth retardation, skeletal abnormalities, photosensitivity RNA is permanently stalled at damage sites and must recruit other repair proteins

Question 40

Pseudogenes

Answer 40

genes accumulated from other organisms that we have silenced

Question 41

RNAi

Answer 41

RNA interference process where RNA molecules (miRNA, micro) inhibit gene expression or translation they neutralize targeted mRNA molecules

Question 42

Long Terminal Repeats

Answer 42

identical sequences of DNA, repeated thousands of times over found at either end of retrotransposons (proviral DNA) is formed by reverse transcription of retroviral RNA is used by viruses to insert their genetic material into the host genome

Question 43

Ionizing radiation

Answer 43

x-rays and their resulting reactive oxygen species

Question 44

Non-ionizing radiation

Answer 44

UV rays which cause pyrimidine dimers to form