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MCM > Exam 2- Fxns and Dysfunction in Genomic Regulation > Flashcards

Exam 2- Fxns and Dysfunction in Genomic Regulation Flashcards

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1
Q

Central dogma of molecular biology

A
  • DNA to RNA via transciption
  • RNA to protein via translation
  • DNA replication via mitosis
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2
Q

meiosis

A

-transfer of genetic information from parent to offspring

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3
Q

exclusive carrier of information from DNA to protein

A

mRNA

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4
Q

RNA virus

A
  • can be reverse transcribed into DNA using reverse transciptase
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5
Q

transcription vs translation

A
  • transcription is DNA to RNA (same language)

- translation if RNA to protein (different language)

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6
Q

structure of DNA

A
  • DNA is double stranded and antiparallel
  • strands connected by hydrogen bonds between nucleotides
  • strands are polar with a 5’ and 3’ end
  • sugar-phosphate backbone forms major and minor grooves
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7
Q

Hydrogen bonds between nucleotides

A
  • G to C has 3 H-bonds

- A to T has 2 H-bonds

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8
Q

importance of condensation of mitotic chromosomes

A
  • mitotic chromosomes are condensed to prevent physical damage to DNA when cells are separated and DNA is passed on to daughter cells
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9
Q

DNA packaging

A
  • DNA is wrapped around histone octamer using hydrogen bonds to form nucleosomes
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10
Q

Histone proteins

A
  • 20% of histone proteins AA residues are Lys or Arg (have NH+ group)
  • Lys and arg are targets of PTM
  • histone proteins are highly conserved across species
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11
Q

nucleosome

A
  • basic unit of chromosome packing

- each nucleosome core consists of a complex of 8 histone proteins

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12
Q

histone octamer

A
  • protein around which DNA is wound

- protein + DNA= chromatin

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13
Q

euchromatin

A
  • lightly packed form of chromatin
  • often under active transcription
  • most active part of genome
  • 92% of human genome is euchromatin
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14
Q

heterochromatin

A
  • very condensed chromatin
  • seemingly genetically inactive
  • highly concentrated at centromeres and telomeres
  • very few active genes, those that are presents are resistant to gene expression
  • position effect: activity of a gene depends on relative position on the chromosome
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15
Q

What information is found on chromosomes?

A

1) genes (encoding proteins and RNA molecules)

2) interspersed DNA that does not contain genes (regulatory information, “junk” DNA)

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16
Q

year watson and crick describe the double helical structure of DNA

A

1953

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17
Q

year nirenberg, khorana and holley determin the genetic code

A

1966

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18
Q

February 2001

A

the sequence of the human genome (human genome project) was announced, it was only 90% completed, finished in 2004

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19
Q

percentage of DNA sequence in exons (protein coding sequences)

A

1.5%

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20
Q

microRNA

A

1) precursor folds back on itself using H bonds
2) Dicer moves along double stranded RNA and cuts it into shorter segment
3) 1 strand of the small segments is degraded and the other associates with a complex of proteins
4) bound miRNA wan base-pair with any target mRNA that contains a complementary sequence
5) miRNA either induce degradation of mRNA or block translation of mRNA

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21
Q

Coding sequences of DNA and RNA

A
  • exons

- they are spliced together out of mRNA

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22
Q

Start/end sequences of introns

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A

intron mRNA sequences start with GT and end with AG 99% of the time

23
Q

Histone deacetylation

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A
  • actively represses gene expression

- deacetylated chromatin is very compact and transciptionally repressed

24
Q

Histone acetylation

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A
  • actively promotes gene expression
  • acetylated chromatin is open and transciptionally active
  • mediated by binding of transcription factors
25
nuclear receptor signaling
- lipophilic ligands (cholesterol derivatives) pass through the PM and nuclear membrane to bind to the DNA and cause transciptional modifications
26
Post translational modifications of histones
- alter histone interactions with DNA and nuclear proteins - histone protein tails are the target of multiple PTMs - most PTM focus on lysine and arginine residues
27
DNA methylation
- methy groups added to DNA by methyl transferase - changes activity of DNA sequence - represses gene transcription when at promoter
28
PTM phosphoylation
often occurs at serine or threonine residues
29
CpG Islands and Methylation
- CpG islands in promoter acquire abnormal hypermethylation - silences gene - can be inherited by daughter cells
30
Hypomethylation
- chromosomal instability | - loss of imprinting
31
nucleoside analog inhibitors
- DNA polymerase requires a primer with a free 3' -OH to begin processing - nucleoside analog inhibitors lack a 3' -OH group and act as drugs that inhibit DNA replication i.e. cytarabine, acyclovir for herpes virus, and AZT for HIV
32
DNA replication is..
- semiconservative - bi directional with replication fork - semi- discontinuous (continuous leading strand synthesis, discontinuous/segmented lagging strand synthesis)
33
Okazaki fragments
segments of DNA from lagging strand during DNA synthesis
34
DNA helicase
- pries apart the helix/unwinds DNA during synthesis | - binds and hydrolyzes ATP
35
Single-stranded DNA binding protein
- binds cooperatively to exposed ssDNA - helps stabilize unwound DNA and straightens DNA - prevents formation of hairpins
36
topoisomerase
- relieves over-wound supercoils - like untangling old phone cord - pharmaceutical drugs that target/inhibit DNA topoisomerase are used as anti-cancer agents (harm integrity of genome- lead to apoptosis)
37
DNA ligase
It has three general functions: It seals repairs in the DNA, it seals recombination fragments, and it connects Okazaki fragments
38
DNA polymerase
are enzymes that create DNA molecules by assembling nucleotides, the building blocks of DNA.
39
Ionizing radiation (x-rays)
can damage DNA by: - DNA strand breaks - chemical modification of bases - DNA and proteins form cross-links
40
nonionizing radiation (UV light)
- can create pyrimidine dimers or 6-4 cross linkages between 2 pyrimidines (thymine dimers)
41
spontaneous DNA damage
- caused by endogenous agents 1) depurination of Adenosine and guanine by removal of their bases (hydrolysis of N-glycosyl linkage) 2) deamination of adenine/guanine/cytosine to generate hypoxanthine/xanthine/uracil - can result in base deletion or substitution
42
Thymine modifications
- formation of thymine dimers | - 6'-4' covalent linkages of thymine bases
43
intercalation
substance inserts itself in between DNA bases and damages DNA (thalidomide)
44
direct repair
- enzymatic repair | - damage repaired: pyrimidine dimers, O6-methylguanine
45
base excision repair (BER)
Damage repaired: single-base mismatches, nondistorting alterations (i.e depurination)
46
nucleotide excision repair (NER)
- damage repaired: chemical adducts that distort DNA( pyrimidine dimers, BPDE-guanine adducts, cisplatin adducts) - associated disorder: Xeroderma pigmentosum
47
mismatch excision repair (MER)
- damage repaired: mismatched base in daughter strand | - associated disorder: Hereditary nonpolyposis colorectal cancers
48
recombination repair/ homologous recombination
- damage repaired: double-strand breaks, interstrand cross-linking - associated disorder: BRCA 1/2 breast cancer
49
transcription coupled repair (TCR)
- damage repaired: stalled RNA polymerase during transcription (not replication) - associated disorder: Cockayne syndrome
50
Xeroderma pigmentosum
phenotype: skin CA, UV sensitivity, neurological abnormalities process affected: nucleotide excision repair
51
Hereditary nonpolyposis colorectal cancer
process affected: mismatch repair
52
Hereditary nonpolyposis colorectal cancer
process affected: mismatch repair | -inherited in an autosomal dominant manor
53
cockayne syndrome
Phenotype: developmental and neurological delay, photosensitivity, and progeria process affected: transciption coupled repair - if DNA is not repaired then this leads to early cell death
54
BRCA associated breast CA
phenotype: breast, ovarian and prostate CA process affected: repair by homologous recombination - BRCA genes are tumor suppressor genes

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