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025. My MCM Test 2 > Genomic Regulation > Flashcards

Genomic Regulation Flashcards

1
Q

What does the nucleus do and what is the total volume of it in a cell?

A

Cell regulation, proliferation, DNA trasncription, 6% total volume of cell

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2
Q

Central dogma of genetics?

A

DNA (replication) -> RNA by transcription -> Protein by translation. RNA can go to DNA by virus

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3
Q

How many bonds do AT and GC make

A

AT makes 2 and GC makes 3

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4
Q

What is important about DNA?

A

Double stranded, antiparallel, nucleotides connected by phosphodiester bonds, and complementary base pair by hydrogen bonds. Has a sugar phosphate backbone. Has major and minor groove

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5
Q

Why are mitotic chromosomes condensed 500 times when compared with interphase chromosomes?

A

To prevent physical damage to DNA as chromosomes are separated and passed onto daughter cells.

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6
Q

Characteristics of Histone proteins?

A
  1. 20% are either lysine or aginine (many +++ charges)
  2. Attracted to - - - charged DNA backbone
  3. Lysine in histone proteins are target of post-translation modifications (PMT)
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7
Q

What are nucleosomes and what do they consist of?

A

Basic unit of chromosome packing, consist of 8 histone proteins and non histone chromosomal proteins… Chromatin = histone + DNA

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8
Q

What is euchromatin?

A

Lightly packed form of chromatin, often under active trasncription, 92% of human genome. Not tightly packed so very active

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9
Q

What is heterochromatin?

A

Very condensed chromatin found at the centromeres and telomeres of chromosome. Packed very tight so not active at all. 8% of human genome

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10
Q

What is the postition effect?

A

Activity a gene depends on relative to the position on the chromosome: activly expressed genes will be silenced if near heterochromatin

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11
Q

What percentage of human genome is responsible for coding (in exons)?

A

1.5%

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12
Q

What test is used to detect genomic differences / abnormalities?

A

Comparative genome hybridization arrays (CGH arrays)

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13
Q

What is RNAi? and what does it do?

A

Interference RNA: a process in which RNA molecules inhibit gene expression or translation by neutralizing target mRNA molecules

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14
Q

What are and where are long terminal repeats LTRs found?

A

repeat same sequences thousands of times, found in retro transposons, formed by retroviral RNA

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15
Q

What does microRNA (miRNA) do?

A

It attaches to protein complexes and degreades mRNA or blocks translation

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16
Q

How do 5 of the same exons code for different proteins?

A

Alternative RNA splicing, 26000 genes encode 100000 proteins, much variability

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17
Q

Introns in RNA splicing….

A

always (99% of the time) start with GT and end with AG

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18
Q

What percent of mutations affect RNA splicing?

A

15%

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19
Q

What do Histone deactylase (HDAC) do to histones?

A

they deacetylate lysine residues, which allows the chromatin to be compact and transcriptionally repressed (OFF)

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20
Q

What do Histone acetylation transferase (HAT) do to histones?

A

They acetylate lysine residues, which opens chromatin and makes it transcriptionally active (ON) – unwinds

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21
Q

What are the purpose for H3 and H4 (core of H2A and H2B can be modified as well) long tails on histones?

A

For post-translational modification (PTM), including mehtylation, acetylation, phosphorylation, etc which target K/R residues.

22
Q

Why is PMT methylation to cytosine and adenine needed?

A

Done by methyl transferase enzymes, it changes the activity of a DNA segment without changing the sequence… represses gene transcription at gene promoter

23
Q

Why is methylation important to cancer?

A
  1. if too methylated at CpG (promoter) causes transcriptional silencing (inherited by daughter cells)
    can also silence oncogene suppressors which will not inhibit cancer growth
24
Q

What is hypo and hypermethylation?

A

Hypo: under-methylation, causes instability and loss of imprinting
Hyper: excess methylation, causes silencing of gene promoters

25
Q

What is the difference between the lagging and leading stand in DNA replication?

A

Leading strand is synthesized continuously, lagging strand is synthesized in segments, known as okazaki fragments.

26
Q

What is DNA helicase and what does it do?

A

It unwinds DNA for replication. Has 6 subunits, binds a hydrolyzes ATP, 1000bp/sec

27
Q

What is single-stranded DNA - binding protein (SSBP) and what does it do?

A

it binds cooperatively to exposed ssDNA (singlestranded). helps stabilize the unwound DNA, prevents hairpins

28
Q

What does topoisomerase do in DNA replication?

A

Relieves overwound supercoilds (called DNA gyrase in bact.)

29
Q

Why do topoisomerase inhibitors act as anti-cancer agents?

A
  1. They block the cell cycle because they are not able to keep the DNA unwound.
  2. They generate single/double stranded breaks
  3. Harms integ of genome
  4. Leads to apoptosis and cancer cell death
30
Q

Why are there so little errors during DNA replication (1 mistake in every 10^9 bp, 3 every human genome)?

A

Because DNA polymerase can proofread! if not caught, will be fixed by repair mechanisms

31
Q

Topoisomerase I and II inhibitors?

A

Irinotecan (colorectal cancer)

Etoposisde, Anthracyclines (Doxo/Daunorubocin) for leaukemia and cardiotoxicity

32
Q

What DNA damage occurs by UV radiation?

A

Production of a covalent linkage between 2 adjacent pyrimidines (T-T C-T) called pyrimidine dimers

33
Q

What DNA damage occurs by ionizing radiation?

A

Double stranded breaks

34
Q

What DNA damage occurs by non-ionizing radiation?

A

Adjacent thymine dimers form

35
Q

What DNA damage occurs spotaneously? and what other products can be formed?

A

Depurination (loss of A/G) 5000 lost a day
Deamination C changed to U, 100 a day
Deamination products: (A) Hypoxanthine, (G) Xanthine, (C) Uracil

36
Q

What is the risk of eating well done meat compared to not well done?

A

Well done is a carcinogen (BPDE a epoxide) which was originally a pre-carcinogen (benzo[a]pyrene)

37
Q

What are cross-linking agents (can cause DNA damage)?

A

Nitrogen Mustard
Cisplatin
Mitomycin C
Carmustine

38
Q

What are alkylating agents (can cause DNA damage)?

A 
dimethyl sulfate (DMS)
methyl methanesulfonate (MMS)
39
Q

What is an important intercalating agent (in between DNA bases)?

A

Thalidomide! cause birth defects in babies when mother took for morning sickness

40
Q

Both outcomes of DNA damage?

A
  1. Repaired = normal function

2. Deleted sequences= impaired fucntion, cell death, mutations/genetic instability (CANCER)

41
Q

3 types of genetic defects in DNA repair pathways?

A

Ataxia telangiectasia (AT)
BRCA2
Fanconi anemia groups A-G

42
Q

What type of DNA damage is repaired by direct repair, and how?

A

Pyrimidine dimers, by using DNA photolyase (photoreactivation)

43
Q

What type of DNA damage is repaired by base excision repair and how?

A

single base mismatches, using glycolases to remove mismatch, AP endonuclease, lyases to remove sugar backbone, DNA polymerase and ligase adds new tide and seals

44
Q

What type of DNA damage is repaired by nucleotide excision repair and how?

A

chemical aducts like pyrimdine dimers, using NER complex (recognizes) nuclease cuts backbone, DNA helicase takes out cut piece, DNA polymerase makes new 12 according to other strand, ligase seals together

45
Q

What type of DNA damage is repaired by mismatch repair, and how?

A

mismatched bases in daughter strands, MER complex binds at mismatch, endonuclease cuts daughter strand, helicase removes seg, poly sigma fills in gap and ligase seals

46
Q

What are the two types of Recombination Repair enzymes, and what is their general job?

A

Damage: double strand breaks.

Non-Homolologous End Joining (NHEJ)
rejoin portions of DNA that have “double strand breaks,” where the entire helix is cut like a string. They join the ends back together.
Homologous Recombination
check a newly created helix of DNA that has been cut against the old helix, and reintroduces any missing nucleotides at the point of the break.

47
Q

What is affect by these factors and process… Development, environmental chemicals, drugs, aging, diet?

A

Epigenetics (mechanisms)

48
Q

What are HDAC inhibitors?

A

vorinostat, entinostat

49
Q

What do trasncription factors do?

A

They talk to eachother, do not work alone!

50
Q

What are the relevance of CpG islands around a start codon?

A

1/10 are CpG. 70% of promoters contain these, this is to let the DNA know that Start is happening soon! if there is hypermethylation, will most likely silence start

51
Q

Methylation of CpG islands do what?

A

occurs at 5 position of cytosine residues, forming 5-methylcytosines, Stably silence genes

025. My MCM Test 2 (15 decks)

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