Study BMB 400 Chapter 9 Flash Cards

 
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BMB 400 Chapter 9

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translesion DNA polymerase
-A widely opened nucleotide binding pocket in the Y-family DNA polymerases allows the enzyme positioning the incoming nucleotide at active site without Watson-Crick base pair with template DNA
Y-family (error-prone) DNA polymerase
synthesizes DNA with template DNA but it is also able to incorporate nucleotide without DNA base-paring (SOS-response)
-Pol IV or Pol V in E. coli
Nonhomologous End Joining (NHEJ) pathway (Fig. 9-18)
does not use a sister chromosome for repair. This repair pathway introduces mutation at the junction.

The NHEJ pathway is ubiquitous in eukaryotes, but less frequently in bacteria
Double-strand break (DSB) repair pathway
uses an homologous recombination with undamaged DNA for repair the double-stranded DNA break without introducing any mutation. (discussed in Chap. 10)
Transcription-coupled repair
The system forces repair enzymes on DNA being actively transcribed. In bacteria, DNA mutation on a template strand for making RNA is repaired more efficient than mutation on a non-template strand.
nucleotide excision repair
-recognize distortions in shape (unlike base excision)
-removes patch
-ssDNA gap
-DNA pol fills in
How do DNA glycosylase detect damaged bases if it is buried in the double helix?
Flipped out damaged DNA base from double helix (Fig. 9-14)
base excision repair
-glycocyase recognizes/removes damaged base by hydrolyzing gylcosidic bond
-abasic sugar removed from backbone
-AP endonuclease cuts DNA backbone
2 principle repair systems
-base excision repair
-nucleotide excision repair
Methyl group removal (Fig. 9-12):
Methyl transferase (e.g., Ada) is a protein for removing mehylgroup from base; it is also a transcription factor (methylated form of Ada) to expressing genes for DNA repairs (Coupling between DNA repair and transcription)
Photoreactivation (Fig. 9-11)
: pyrimidine dimer is made by an energy of light. The repair enzyme (DNA photolyase) also uses an energy of light for repair it.
Gamma radiation and X-ray (ionizing radiation):
double-strand DNA breaks (which is difficult to repair)
Ultraviolet light:
thymine dimmer, unable of base paring and stop DNA polymerase and also RNA polymerase
Alkylation:
Methyl or ethyl groups are transferred to bases
Hydrolytic damage:
spontaneously deamination of cytosine, adenine and guanine
Dam methylase
methylates A residues of GATC sequence
-only parental strand methylated for a while
-until Dam catches up, only template methylated
mismatch repair system corrects the mismatch only in the newly synthesized DNA?
Solution: using DNA methylation as a marker to identify an newly synthesized DNA strand (e.g. Dam methylase)
-MutH makes incision in unmyethylated daughter strand
MutS/MutL/MutH system in E. coli
-system scans whole genome to fine mismatch
-The MutS recognizes unusual DNA structure (DNA bending) because of the mismatch base pairing instead of directly monitor the DNA mismatch. The MutS uses ATP as a cofactor.
Mismatch repair increases accuracy of DNA synthesis by an additional x100~1000
Q. What is an error rate of the replicative DNA polymerase?
DNA mutation
produces mismatch in first round of replication and permanently incorporates in second round replication
DNA microsatellites:
mutation-prone sequence, di-, tri- or tetranucleotide sequenes
e.g. CA repeats in human genome, it causes DNA synthesis slippage to increase number of copies of repeated sequences
“Hot spot”:
mutation arise at high frequency
Transversions:
pyrimidine-to-purine and purine-to-pyrimidine
Transitions:
pyrimidine-to-pyrimidine and purine-to-purine
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