genomic functions Flashcards
What is the base excision repair mechanism?
For single base mismatches that don’t distort (DNA polymerase does this)
DNA glycosylase detects and removes the mismatched base.
AP endonuclease cuts the phosphodiester bond
AP lyase removes the deoxyribose phosphate
DNA polymerase Beta replaces the nucleotide
DNA ligase seals the nick
What is the mechanism for nucleotide excision repair? (often chemically induced damage like thiamine dimers)
NER complex recognizes distortions and nicks DNA on both sides of the distorting adduct.
DNA polymerase then fills the gap
DNA ligase seals the nick
Describe transcription-coupled repair
When RNA polymerase is stalled at lesions in DNA it directs repair machinery to it.
Describe Mismatch repair
MER complex binds to DNA, recognizes mismatch in daughter strand, then cuts the segment
DNA polymerase and ligase fill and seal the gap.
How is DNA packaged and unwound by histones?
Lys and Arg are positive (1/5 of histone), DNA negative charge
Histone acetylation: loosely packed for transcription by removing positive charge
Histone methylation: loosely packed for transcription by physical interference
describe how histones are modified
HIstones have tails upon which various enzymes work.
Writer enzymes add modifications
Eraser enzymes remove them
Reader enzymes bind to the modification to further alter gene activity
Helicase
unwinds DNA helix
ATP fuels it
Topoisomerase
Relieves over-wound supercoils;
reversible
DNA polymerase a
In complex with primase.
Synthesizes RNA-DNA primer
DNA polymerase d and e
Synthesize new DNA chain in the 5to3 direction
Flap endonuclease 1
REmoves RNA primers
DNA polymerase d
Fills in gaps
DNA ligase
seals nicks
What enzyme is inhibited during DNA replication?
Topoisomerase is inhibited by
Etoposide in eukaryotes
Flouroquinolones in prokaryotes
What is the relationship between telomeres and telomerase?
telomeres are the primers for replication. When the primer runs out then the cell cannot replicate more DNA
Telomerase restores the lost primer each division. It has a RNA template for reverse transcription. One step that cancer must accomplish is further activation of telomerase
What causes pyrimidine dimers?
UV radiation causes adjacent pyrimidines to form covalent bonds
What is the problem involving methylated cytosines?
If C is methylated then it often spontaneously is converted to T. In CpG islands there is a high frequency of methyl-C. This methylation silences Cancer/DNA repair genes. If converted to T often in the island then silencing is ineffective.
Name some cross linking agents
Nitrogen mustard, Cisplatin, Mitomycin C, Carmustine
Name some alkylating agents:
Dimethyl sulfate (DMS) Methyl mehanesulfonate (MMS)
Name some Intercalating agents.
Ethidium bromide
Thalidomide
Doxorubicin
Daunomycin
Direct repair
pyrimidine dimer repair and methylguanine repair
DNA photolyase
Methylguanine methyltransferase