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MCM > Genomic Regulation, Theisen > Flashcards

Genomic Regulation, Theisen Flashcards

1
Q

Microarray

A

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

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2
Q

tRNA

A

transfer AA to ribosome for protein synthesis

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3
Q

mRNA

A

codes for proteins

contains the base pairs for AA

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4
Q

rRNA

A

structural RNA

combines with proteins to form ribosomes

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5
Q

snRNA (small nuclear)

A

part of spliceosomes

involved in splicing of precursor mRNA

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6
Q

scRNA (small cytoplasmic)

A

involved in protein processing and secretion

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7
Q

RNaseP (ribonuclease P)

A

a catalytic RNA (ribozyme)

involved in cleavage and removal of extra RNA sequence

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8
Q

siRNA (short interfering)

A

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

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9
Q

miRNA (micro)

A

involved in post transcriptional regulation of gene expression
associated with diseases

ex: iRNA

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10
Q

Alternative Splicing

A

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

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11
Q

RNA interference

A

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

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12
Q

DNA transposon

A

elements in our own genome

long repetitive sequences

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13
Q

LTR retrotransposons

A

acts more like a virus/retrovirus

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

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14
Q

Non-LTR retrotransposons

A

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

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15
Q

Retrotransposons

A

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

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16
Q

Euchromatin

A

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

ex: GAPDH, ATCase, HGPRT

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17
Q

Heterochromatin

A

very condensed chromatin
contain more viral transposons
have less used information

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18
Q

Histone acetylation

A

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)

19
Q

Histone methylation

A

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

creates an increase in transcription

20
Q

Histone/Nucleosome info

A

there are 8 histone proteins

each nucleosome has 4 proteins in it

21
Q

DNA methylation

A

methyl group opens up the DNA by creating physical interference

usually silences transcription
can be inheritable (cancer)

accumulation of methyl groups is passed down

22
Q

Helicase

A

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

23
Q

Topoisomerase

A

a reversible enzyme

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

relieves supercoiling due to helicase action

24
Q

Telomeres

A

found at the end of chromosome strands for protection

shorten over time due to aging

25
Q

Telomerase

A

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

26
Q

Intercalating agents

A

high affinity for DNA and cause replications and fidelity when attached

ex: thalidomide, ethidium bromide

27
Q

Direct Repair (enzymatic repair)

A

Damage repaired:

  • pyrimidine dimers
  • O6 methylguanine

Enzymes/mechanism/disorder:

  • DNA photolyase cuts pyrimidine dimers using visible light
  • methylguanine methyltransferase removes methyl group
28
Q

Base excision repair (BER)

A

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
29
Q

Nucleotide excision repair (NER)

A

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

30
Q

Mismatch excision repair (MER)

A

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

31
Q

Recombination Repair

  • nonhomologous (NHEJ)
  • homologous
A

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

32
Q

Transition coupled repair (TCR)

A

Damage repaired:
-stalled RNA polymerase during transcription

Enzymes/mechanism/disorder:
-recruits other repair proteins

Disease: Cockayne Syndrome

33
Q

Translesion Synthesis (bypass synthesis)

A

Damage repaired:
-unrepaired thymine dimers or apurini AP sites

Enzymes/mechanism/disorder:
-DNA polymerases (reduced fidelity polymerases)

34
Q

Spontaneous DNA Damage

A

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

35
Q

CPG Islands/CPG Sites

A

adjacent cytosine-phosphate-guanine

methylation of these islands to the cytosine is problematic

this causes silencing of genes (Cancer/DNA repair genes)

36
Q

Xeroderma pigmentosum

A

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

37
Q

Hereditary non-polyposis colorectal cancer

A

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

38
Q

BRCA1/BRCA 2: Breast Cancer

A

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

39
Q

Cockayne’s Syndrome

A

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

40
Q

Pseudogenes

A

genes accumulated from other organisms that we have silenced

41
Q

RNAi

A

RNA interference

process where RNA molecules (miRNA, micro) inhibit gene expression or translation

they neutralize targeted mRNA molecules

42
Q

Long Terminal Repeats

A

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

43
Q

Ionizing radiation

A

x-rays and their resulting reactive oxygen species

44
Q

Non-ionizing radiation

A

UV rays which cause pyrimidine dimers to form

MCM (6 decks)

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