Mismatch Repair in E. coli

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Questions and Answers

What is one primary role of mismatch repair in DNA?

To enhance genetic recombination

To promote sister chromatid exchange

To increase the rate of DNA synthesis

To correct mutations arising from replication errors (correct)

How does mismatch repair determine which DNA strand to repair?

By identifying adenine methylation at specific sequences (correct)

By comparing the methylation of both strands equally

By examining the presence of thymine modifications

By recognizing the oldest strand in the DNA helix

What happens to mutation production when any of the E. coli mutator genes are inactivated?

Mutation production becomes negligible

Mutation production remains stable

Mutation production increases significantly (correct)

Mutation production decreases dramatically

What state does newly synthesized DNA have that directs mismatch repair?

It is transiently unmodified Signup and view all the answers

Which of the following is NOT one of the E. coli mutator genes involved in mismatch repair?

mutX Signup and view all the answers

What does the mismatch repair system primarily target during DNA replication?

Mismatched base pairs produced by errors Signup and view all the answers

What discovery by Pat Pukkila contributed to understanding mismatch repair in E. coli?

The influence of adenine methylation on repair direction Signup and view all the answers

Why is mismatch repair considered crucial for genetic stability?

It corrects biosynthetic errors in DNA Signup and view all the answers

What is the primary function of the MutS protein?

To recognize mismatched base pairs Signup and view all the answers

What is the purpose of the strand break in the methyl-directed mismatch repair system?

To provide a signal for repair Signup and view all the answers

How is MutL recruited to the MutS-mismatch complex?

In an ATP-dependent reaction Signup and view all the answers

Which protein has a latent endonuclease activity that is activated by the MutL-MutS-heteroduplex complex?

MutH Signup and view all the answers

What happens to the DNA strand at the site of a nick when subjected to repair?

Only the nicked strand undergoes repair Signup and view all the answers

Which organisms' cell extracts were used to demonstrate DNA repair on nicked strands?

Human and Drosophila melano-gaster Signup and view all the answers

What is the nature of the endonuclease activity exhibited by MutH?

Very tightly associated, nearly inactive Signup and view all the answers

What role does UvrD play in the mismatch repair process?

DNA unwinding Signup and view all the answers

What characterizes the phenotype known as microsatellite instability?

High frequency of mutation in simple repeat sequences Signup and view all the answers

What key discovery was made regarding certain cancers linked to microsatellite instability?

They are characteristic of Lynch syndrome. Signup and view all the answers

What is the significance of the crystal structure of the E.coli MutS dimer bound to a G-T mismatch?

It provides evidence for mismatch recognition by MutS Signup and view all the answers

What fundamental aspect differentiates the human mismatch repair mechanism from that of E.coli?

The proteins involved in initiating repair Signup and view all the answers

Which protein is specifically identified as an exonuclease required for mismatch repair?

Exonuclease I Signup and view all the answers

What previous work confirmed that the uvrD gene product is DNA helicase II?

Research by Peter Emmerson Signup and view all the answers

In the context of DNA repair, when both DNA strands are covalently continuous, what is the observed outcome?

Repair is entirely blocked Signup and view all the answers

What did Woei-horng Fang demonstrate about DNA hydrolytic events in relation to the nick and mismatch?

They are restricted to the shorter path between the nick and the mismatch. Signup and view all the answers

Which organization is acknowledged for its support of the mismatch repair studies?

The Howard Hughes Medical Institute Signup and view all the answers

What is one of the key topics discussed in the acknowledged research?

Mismatch repair mechanisms Signup and view all the answers

Which of the following is a publication referenced in the acknowledgments?

Chromosome breakage accompanying genetic exchange in bacteria Signup and view all the answers

Which of the following authors contributed to the studies of recombining DNA in pneumococcal transformation?

Ephrussi-Taylor, H. Signup and view all the answers

What mutation mechanism is highlighted in the referenced study by Rydberg, B.?

Bromouracil mutagenesis Signup and view all the answers

Which type of DNA is discussed in the context of mismatch repair mechanisms?

Heteroduplex DNA Signup and view all the answers

What was a significant finding in the research related to DNA adenine methylation?

It affects methyl-directed mismatch repair. Signup and view all the answers

Which of the following studies was conducted by Glickman, B.W. and Radman, M.?

Escherichia coli mutator mutants and their effects on mismatch correction Signup and view all the answers

Which role does the zinc finger motif in human replication protein A play in DNA processes?

Required for DNA replication Signup and view all the answers

What is the primary function of PCNA in human mismatch repair?

Involvement in a step preceding DNA resynthesis Signup and view all the answers

What is necessary for human mismatch repair according to the studies mentioned?

DNA polymerase delta Signup and view all the answers

Which component enhances the mismatch dependence of 5'-directed excision in human mismatch repair?

PARP-1 Signup and view all the answers

What type of reaction does the reconstitution of human mismatch repair support?

Nick-directed bidirectional reaction Signup and view all the answers

What system supports bidirectional mismatch-provoked excision?

A defined human system Signup and view all the answers

Which process is NOT influenced by the zinc finger motif of human replication protein A?

Nucleotide excision repair Signup and view all the answers

Which research focused on characterizing the role of human replication protein A in mismatch repair?

Ramilo et al. (2002) Signup and view all the answers

Study Notes

Mismatch Repair

Mismatch repair is a crucial process in DNA replication, correcting errors in DNA synthesis
The primary function is to identify and eliminate these errors, ensuring genetic stability
This system identifies newly synthesized DNA strands, distinguished by their transient lack of methylation
This lack of methylation, specifically at d(GATC) sequences, directs the repair machinery

Methyl-Directed Mismatch Repair in E. coli

In E. coli, the methyl-directed mismatch repair pathway relies on four key proteins: MutH, MutL, MutS and UvrD
MutS binds to mismatched base pairs, initiating the repair process
MutL is recruited to the MutS-mismatch complex in an ATP-dependent manner
MutH has endonuclease activity that specifically targets unmethylated d(GATC) sequences
UvrD, known as DNA helicase II, unwinds the DNA helix in an ATP-dependent manner

Bidirectional Excision

The methyl-directed mismatch repair pathway in E. coli involves bidirectional excision
This means that DNA repair happens in both directions around the mismatch site, which helps to ensure complete repair

Human Mismatch Repair: Similarities and Differences

Human mismatch repair shares features with the E. coli system, yet operates with distinct mechanisms
Human cells use a specific nick in the DNA strand as a signal for repair
This nick directs repair activities to the shorter path between the nick and the mismatch site
Human cells utilize DNA polymerase delta to ensure accurate synthesis during the repair process

Microsatellite Instability and Lynch Syndrome

Microsatellite instability, characterized by frequent mutations in repetitive DNA sequences, is a hallmark of certain cancers
Lynch Syndrome, a hereditary cancer predisposition, is associated with microsatellite instability
These findings emphasize the crucial role of mismatch repair in cancer prevention and development

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Description

Explore the essential process of mismatch repair in DNA replication, focusing on its importance for genetic stability. This quiz covers the specific mechanisms and key proteins involved in the methyl-directed mismatch repair pathway in E. coli, including MutH, MutL, MutS, and UvrD.