DNA Repair Mechanisms Overview
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Questions and Answers

What role does methylation play in mismatch repair?

  • It facilitates DNA polymerase activity.
  • It marks the newly synthesized strand.
  • It is used to identify the parental strand. (correct)
  • It signals when to initiate excision repair.

Which mutagen leads to the formation of pyrimidine dimers?

  • High-energy ionizing radiation
  • Base analogs
  • Alkylating agents
  • Nonionizing radiation (correct)

What is the first step involved in the excision repair systems?

  • Removal of the damaged segment.
  • Ligation of the repaired strand.
  • Recognition of the damage. (correct)
  • Replacement of the damaged nucleotide.

During mismatch repair, which proteins are responsible for identifying mispaired nucleotides in E. coli?

<p>Mut proteins (A)</p> Signup and view all the answers

What happens to the DNA strand after it is nicked during mismatch repair?

<p>Additional nucleotides at both ends are removed. (A)</p> Signup and view all the answers

How does the process of homologous recombination assist in DNA repair?

<p>It provides a template for DNA synthesis. (A)</p> Signup and view all the answers

What is a primary effect of chemical mutagens like nitrous acid?

<p>They deaminate cytosine to uracil. (B)</p> Signup and view all the answers

What distinguishes the new DNA strand from the parental strand during mismatch repair?

<p>The level of methylation (D)</p> Signup and view all the answers

What is the primary consequence of the inability to repair DNA in xeroderma pigmentosum?

<p>Accumulation of mutations leading to cancer (C)</p> Signup and view all the answers

Which repair mechanism is characterized by the loss of some DNA during the repair process?

<p>Nonhomologous end-joining (NHEJ) (B)</p> Signup and view all the answers

Which proteins are primarily involved in the nonhomologous end-joining repair mechanism?

<p>Ku proteins (C)</p> Signup and view all the answers

What distinguishes homologous recombination from nonhomologous end-joining?

<p>Presence of template DNA for error-free repair (A)</p> Signup and view all the answers

What is a common risk associated with defects in the nonhomologous end-joining repair system?

<p>Predisposition to cancer and immunodeficiency syndromes (D)</p> Signup and view all the answers

Which of the following statements about nucleotide excision repair is true?

<p>It is primarily used to fix UV-induced pyrimidine dimers. (D)</p> Signup and view all the answers

In which common genetic condition are mutations in the BRCA1 or BRCA2 proteins linked to increased cancer risk?

<p>Breast cancer susceptibility (C)</p> Signup and view all the answers

What is the role of sensors in the DNA double-strand break repair mechanism?

<p>To identify and recognize double-strand breaks (A)</p> Signup and view all the answers

What is the role of DNA ligase in the synthesis of DNA?

<p>It joins the 3 –OH of newly synthesized DNA to the 5 -P of the original DNA strand. (D)</p> Signup and view all the answers

What genetic condition is associated with mutations in the proteins involved in mismatch repair?

<p>Lynch syndrome (HNPCC). (D)</p> Signup and view all the answers

Which enzyme is primarily responsible for cleaving the N-glycosidic bond in base excision repair?

<p>DNA glycosylase. (A)</p> Signup and view all the answers

What is the result of UV light exposure on DNA?

<p>It causes covalent joining of adjacent pyrimidines to form dimers. (C)</p> Signup and view all the answers

What is an AP site in the context of DNA repair?

<p>A site that lacks a base due to damage. (A)</p> Signup and view all the answers

Which of the following correctly describes nucleotide excision repair in relation to ultraviolet-induced damage?

<p>It involves the recognition and cleavage of dimerized bases. (A)</p> Signup and view all the answers

Which of the following bases is cleaved by DNA glycosylases during base excision repair?

<p>Cytosine to hypoxanthine. (D)</p> Signup and view all the answers

What is the first step in repairing a thymine dimer caused by UV light?

<p>A UV-specific endonuclease recognizes and cleaves the dimer. (B)</p> Signup and view all the answers

Flashcards

DNA Repair

The process of fixing damaged DNA caused by environmental factors or replication errors.

Mutation

A permanent change in the DNA sequence.

Mismatch Repair (MMR)

A DNA repair system that corrects mistakes made during DNA replication.

Methylation

Adding a methyl group to a base, often used to distinguish the original DNA strand from the newly synthesized strand.

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Methylated GATC Sequence

A sequence of four bases (guanine, adenine, thymine, and cytosine) modified by the addition of a methyl group on the adenine.

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Base Analogs

Chemical mutagens that mimic naturally occurring bases, leading to direct mutagenesis.

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DNA polymerase in MMR

Essential enzyme that fills DNA gaps using sister strand as a template.

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Mismatch

A sequence error in DNA caused during replication.

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DNA Ligase Function

DNA ligase joins the 3'-OH end of a newly synthesized DNA strand to the 5'-P end of the pre-existing strand.

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Mismatch Repair Deficiency

Mutations in mismatch repair proteins can cause hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, increasing the risk of colon cancer.

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Base Excision Repair (BER)

BER is a DNA repair pathway that fixes damaged/altered bases.

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DNA Glycosylase Role

DNA glycosylases are enzymes that recognize and remove damaged DNA bases.

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AP Site Formation

An apurinic/apyrimidinic (AP) site is a location in a DNA strand where a base has been removed, leaving a sugar-phosphate backbone.

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Nucleotide Excision Repair (NER)

NER repairs bulky DNA lesions, such as thymine dimers, by removing a segment of the damaged DNA strand.

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Thymine Dimer Formation

UV light causes adjacent thymine bases to form covalent bonds, creating thymine dimers.

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UV-Induced DNA Damage

Exposure to UV light can cause covalent cross-links between DNA strands, preventing proper DNA replication.

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Nucleotide Excision Repair

A DNA repair pathway that removes damaged DNA segments, including those caused by UV radiation. It then uses the undamaged strand as a template to fill in the gap.

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Pyrimidine Dimers

Structural abnormalities in DNA caused by UV light, where adjacent pyrimidine bases (like thymine) bond together.

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Xeroderma Pigmentosum (XP)

Inherited disease where cells cannot repair DNA damage from UV radiation, leading to extreme sensitivity to sunlight and high risk of skin cancer.

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Double-strand Break (dsDNA) Repair

A repair mechanism for DNA damage where both strands are broken, requiring a different approach than for single-strand damage.

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Nonhomologous End Joining (NHEJ)

Method of dsDNA repair where DNA ends are directly rejoined, often with some loss and mutations of DNA.

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Homologous Recombination (HR)

More accurate method of dsDNA repair using a homologous template to direct the repair process, maintaining DNA sequence accuracy.

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BRCA1/2

Genes involved in Homologous Recombination (HR) DNA repair, mutations increase risk of breast cancer.

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DNA Repair Defects & Disease

Defects in DNA repair pathways can lead to increased susceptibility to cancer and other diseases.

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Study Notes

DNA Repair Mechanisms

  • DNA is constantly exposed to environmental insults, causing nucleotide base alterations or removal.
  • Unrepaired damage leads to mutations, potentially causing cell proliferation issues, including cancer.

Physical Mutagens

  • High-energy ionizing radiation (X-rays, gamma rays) causes strand breaks and base/sugar destruction.
  • Non-ionizing radiation (UV light) produces pyrimidine dimers.

Chemical Mutagens

  • Base analogs directly cause mutations.
  • Nitrous acid deaminates cytosine to uracil.
  • Alkylating agents and intercalating agents trigger DNA lesions, leading to indirect mutagenesis.

DNA Repair Systems

  • Many repair systems share similar steps:
    • Recognize the damaged DNA lesion.
    • Remove the damaged portion.
    • Replace the missing segment using the sister strand as a template and synthesize new DNA.
    • Ligation of the repaired strand.
  • Excision repair systems remove one to tens of nucleotides.

Mismatch Repair (MMR)

  • MMR fixes replication errors where one or more bases are mismatched.
  • In E. coli, MMR is mediated by Mut proteins.
  • Similar proteins exist in humans, with a key difference being that in E. coli, the template strand needs to be marked (methylated), whereas in humans it may not.
  • The newly synthesized strand is typically identified and repaired.
  • MMR proteins recognize the mismatch, identify the new strand, remove the error segment, and replace it.

Base Excision Repair (BER)

  • BER corrects damaged bases by removing the damaged segment and then replacing it.
  • Initiated by DNA glycosylase, which recognizes and removes the damaged base.
  • The damaged base is removed by an AP endonuclease and repaired/replaced.
  • DNA glycosylases recognize and remove bases, such as uracil, hypoxanthine, and xanthine.

Nucleotide Excision Repair (NER)

  • NER corrects bulky DNA damage, such as pyrimidine dimers caused by UV light.
  • NER identifies, removes damaged oligonucleotide segment and then replaces it with new DNA.
  • UvrABC proteins are involved in bacterial NER.
  • A similar pathway exists in humans.

Xeroderma Pigmentosum (XP)

  • XP is a rare genetic disorder where cells cannot repair damaged DNA, caused by UV radiation.
  • XP results in an accumulation of mutations and numerous skin cancers.
  • Defects in genes coding for XP proteins involved in nucleotide excision repair cause the disease.

Repair of Double-Strand Breaks (DSBs)

  • Ionizing radiation or oxidative free radicals cause DSBs, which cannot be repaired by methods used for single strand breaks.
  • DSBs are repaired using either:
    • Non-homologous end joining (NHEJ): error-prone pathway that joins the ends of broken DNA without using a template. It can be associated with cancer and immunodeficiency syndromes.
    • Homologous recombination (HR): preferred method. utilizes a homologous sequence to repair broken DNA. Less error prone. Mutations in proteins involved in HR, such as BRCA1 or BRCA2, increase risk of breast cancer.
  • Mechanisms involve proteins that identify, process, and ligate broken DNA ends, as well as utilize the proper template regions for correct reconstruction of the break.

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DNA Repair Mechanisms PDF

Description

Explore the various DNA repair mechanisms that protect the cell from damage caused by physical and chemical mutagens. Learn how these systems function to recognize and fix DNA lesions to prevent mutations and potential cancer development. This quiz will delve into the roles of different types of mutagens and the intricacies of repair systems.

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