BIOL253 L7

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  • Created by: Katherine
  • Created on: 09-04-17 21:29
What is the purpose of mismatch repair?
To correct mistakes made during replication, using the parental strand as a template.
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A mismatch repair system must:
Recognise mismatched base pairs, Discriminated between the correct (parental strand) base and the incorrect (daughter strand) base in a mismatched pair. Excise the incorrect base and carry out repair synthesis.
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What repair system operates in bacteria?
MutSLH
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MutS and MutL proteins are...
Highly conserved - they're found everywhere
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What is the role of MutS?
Recognising the mismatch
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How does MutS?
It circles the DNA and looks for mismatches
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What is the MutSLH repair pathway?
Mut L and Mut H assemble at site of the mismatch in newly synthesised DNA with MutS. The 2nd lobe of Mut L interacts with Mut H at a hemimethylated GATC site, leading to the formation of the Mut SLH complex.
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What happens after the formation of the Mut SLH complex?
Mut H is activated and nicks the newly synthesized unmethylated strand. DNA including themismatch is degraded by a 5' -3' exonuclease assisted by the helicase UvrD.
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What happens after the missmatch is degraded?
Resynthesis of DNA closes the gap, correcting the mismatch
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Mismatch repair system can also correct...
Replicative insertions and deletions.
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Why mights a repetitive region of DNA be skipped during replication?
Because repetitive regions of DNA can form hairpins on the template strand.
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What does skipping of repetitive reions of DNA result in?
Repeat contraction after the next replication round.
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How does mismatch repair respond to hairpins?
It can detect and repair them - the newly synthesised DNA is degrade, the hair pins unfold and the new strand can be re-made.
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What do defects in mismatch repair lead to
Increased rates of spontaneous mutation and cancer
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What is base excision repari?
It has a key role in repairing endogenous damage (2 step process)
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What are cellular glcosylases/
They're specific for certain types of damage.
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What is a failsafe glycosylase?
T;G mismatch glycosylase
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What do hlyosylases do?
They recognise the DNA by going along the chain and clipping out the damaged base.
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What is the second stage of base excision repair?
To induce a nick into the DNA that has an AP site.
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What is an AP endonuclease/
A sugar with nothing attached to it. It cuts either side of the empty sugar - You get a gap in the DNA molecule.
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What is nucleotide excision repair
You cut out an oligonucleotide - it is a mmultifunctional DNA repair sytem. It deals with any damage that distorts the helix.
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In bacteria, nucleotide excision repair is mediated by proteins called...
Uvr proteins (Uvra, Uvrb and Uvrc)
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How do Uvr proteins work?
Bulky DNA regions are recognised by a complex with 2 Uvra and 2 Uvrb proteins. Opening of DNA around damage site by UvrBhelicase and release of UvrA.
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What does Uvrb do?
It opens up the DNA around the damage and recruits UvrC
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What does Uvrc do/
It nicks the famaged DNA, damaged DNA is then removed by UvrD, and DNA is resynthesized from the undamaged strand.
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Are nucleotide excision proteins conserved?
No - not conserved between bacteria and eukaryots but the mechanism is conserved.
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Where does NER operate?
Anywhere in the genome
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Damage in genes that are actively transcribed in...
Preferentially repaired (transcription coupled repair; TCR)
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TCR removes...
Stalled RNA polymerases
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What do individuals with Xeroderma Pigmentosum have
Inherited NER defects (so defects in excision repair). They are sun sensitive, have a predisposition to skin cancer as their is a lack of UV damage repair.
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How many people are affected by Xeroderma Pigmentosum worldwide/
1 in 250000
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Other cards in this set

Card 2

Front

A mismatch repair system must:

Back

Recognise mismatched base pairs, Discriminated between the correct (parental strand) base and the incorrect (daughter strand) base in a mismatched pair. Excise the incorrect base and carry out repair synthesis.

Card 3

Front

What repair system operates in bacteria?

Back

Preview of the front of card 3

Card 4

Front

MutS and MutL proteins are...

Back

Preview of the front of card 4

Card 5

Front

What is the role of MutS?

Back

Preview of the front of card 5
View more cards

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