genomic regulation Flashcards
3 nucleoside analog inhibitors
ara-C (cytarabine) becomes ara-CTP and inhibits DNA polymerase. treats leukemia.
acyclovir (gets phosphorylated by host) and AZT (treats HIV) both lack 3’ OH group so they arrest viral DNA synthesis by acting as chain terminators.
if CpG islands in promoter are methylated…
silences genes.
if this happens to gonads/sperm, methylation is passed on to progeny.
often methylated due to stress
cross linking agents (cross link DNA and protein)
nitrogen mustard, cisplatin, mitomycin C, carmustine
alkylating agents (denature DNA)
dimethyl sulfate (DMS), methyl methanesulfonate (MMS)
intercalating agents (break NA through adding structural change)
thalidomide
direct repair
- repairs pyrimidine dimers and O6 methylguanine
- uses DNA photolyase and methylguanine methyltransferase
base excision repair
- repairs single base mismatches or depurination
- uses DNA glycosylase, AP endonuclease, DNA pol, AP lyase, DNA ligase
nucleotide excision repair
- repairs chemical adducts that distort DNA (ex. pyr dimers)
- uses NER protein complex, DNA pol, DNA ligase
- ->Xeroderma pigmentosum
mismatch excision repair
- repairs mismatched base in daughter strand
- uses MER complex (MutS and MutL), helicase/endonuclease, DNA pol, DNA ligase
- ->Hereditary nonpolyposis colorectal cancer
recombination repair
-repairs double stand breaks, interstrand cross linking (nonhomologous end joining, homologous recombination)
- NHEJ: with damaged ends filled/joined, DNA ligase
- homologous recombo: w/ exonucleases, DNA pol, MER (uses info from normal DNA pair to fix)
–>BRCA mutations and breast cancer
transcription-couples repair
- repairs stalled RNA pol during transcription
- ->Cockayne syndrome
translesion synthesis (bypass synthesis)
- repairs unrepaired thymine dimers or apurinic AP sites
- uses DNA pol
inhibitors of Histone deacetylases
valproic acid, vorinostat
what does rifampicin do?
- inhibits bacterial RNA synthesis
- side effects: increases hepatic cytochrome P-450 enzymes (they add OH to make drugs more soluble, they metabolize drugs), thus increasing metabolism of other drugs and hormones. RED COLOR in urine, sweat, tears for a short time.
imprinting
when methylation/non-methylation can be passed down (think CpG islands)