(L11) Genomic Regulation Flashcards
What is the effect of histone acetylation and deacetylation?
L11 S55
Acetylation: Activate
Deacetylation: Deactivates
What is the effect of ionizing radiation on DNA?
L11 S65
Double stranded breaks
Base modification
DNA-protein cross-links
What is non-ionizing radiation and what does it cause?
L11
Sunlight is the main non-ionizing radiation
Thymine dimers are a result
What are the main types of spontaneous DNA damage?
L11 S67
Depurination:
- loss of G base leaving only sugar and phosphate
- results in loss of base pair (frame shift)
Deamination:
- loss of amine group from C to form U
- results in change of G to an A on newly synthesized strand
What are CpG islands and what is significant about methylated CpG islands?
L11 S71
Adjacent C and G nucleotides
Found around 70% of promotors and, when methylated, stably silence genes
What are DNA cross-linking agents?
L11 S74
- nitrogen mustard
- carmustine
- cisplatin
- mitomycin C
What are alkylation agents?
L11 S74
- dimethyl sulfide (DMS)
- methyl methanesulfonate (MMS)
What are intercalating agents?
L11 S74
- ethidium bromide
- thalidomide
What is base excision repair?
What proteins are involved?
L11 S81
- DNA glycosolases (multiple types) look for altered bases
- base is “flipped out” and glycosyl bond is cleaved
- AP (apurininc/apyrimidinic) endonuclease and phosphodiesterase remove backbone
- DNA polymerase and ligase fill and seal gap
What is nucleotide excision repair?
What proteins are involved?
L11 S83
- enzyme complex looks for lesions/distortions in the double helix
- backbone is cleaved on either side of he damage
- helicase “peels” the damaged DNA off
- DNA polymerase and ligase fill and seal the gap
What is mismatch excision repair?
What proteins are involved?
L11 S85
Removes most of the mismatched base pairs that were missed by proofreading.
MutS (MSH2/6) binds newly synthesized DNA at sites of mismatch.
MutL scans for nicks further along on the DNA (nicks indicate newly synthesized strand vs. original strand).
The newly synthesized strand is removed and resynthesized.
What is nonhomologous end joining?
What changes are made to the DNA sequence?
L11 S89
Ends of break are degraded and are ligased back together.
This results in a loss of the degraded DNA sequences.
What is homologous recombination?
What changes are made to the DNA sequence?
L11 S88
Ends of break are degraded and sister chromatid is used as template to resynthesize missing segment.
This does NOT result in a loss of the degraded DNA sequences.
What is the result of failure to repair a double stranded break?
L11 S90
Portion of a chromosome would no longer have a centromere and origin of replication.
It would also lack protection (telomeres) on the broken ends and would be vulnerable to DNase activity.
What is transcription coupled repair?
What is significant about where it can detect damage?
L11 S91
RNA polymerase stall at lesions in DNA and will direct DNA repair mechanisms to the site.
Can only detect damage on the strand being transcribed, damage on the other strand will go undetected.
