Biochemistry

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Base excision repair

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Biochemistry

Definition

Base excision repair is a crucial cellular mechanism that corrects DNA damage by removing and replacing damaged or non-canonical bases. This process ensures genomic stability and prevents mutations that can lead to various diseases, including cancer. It specifically targets small-scale damage like deamination, oxidation, and alkylation, which can disrupt normal base pairing.

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5 Must Know Facts For Your Next Test

  1. Base excision repair primarily deals with non-helix-distorting lesions, such as uracil incorporation or oxidative damage.
  2. The process begins with the action of DNA glycosylases, which identify and remove the damaged base, creating an AP site.
  3. Following base removal, an AP endonuclease cuts the DNA backbone at the AP site, creating a nick that is then processed by other enzymes.
  4. DNA polymerase then fills in the gap with the correct nucleotide, followed by DNA ligase sealing the nick to restore the DNA strand.
  5. This repair pathway is essential for maintaining genomic integrity and preventing mutations that can result in cancer and other genetic disorders.

Review Questions

  • What role do DNA glycosylases play in the process of base excision repair?
    • DNA glycosylases are essential enzymes in base excision repair as they identify and remove damaged bases from the DNA strand. Each glycosylase is specific to certain types of damage, ensuring that various forms of DNA lesions can be efficiently recognized. Once a damaged base is removed, it results in an apurinic/apyrimidinic (AP) site, which is critical for subsequent steps in the repair process.
  • Describe the steps involved in base excision repair from the removal of a damaged base to the restoration of the DNA strand.
    • The base excision repair process begins with a DNA glycosylase recognizing and removing a damaged base, creating an AP site. This AP site is then cleaved by AP endonuclease, resulting in a break in the DNA backbone. Next, DNA polymerase adds the correct nucleotide to fill in the gap left by the missing base, and finally, DNA ligase seals the break to restore the integrity of the DNA strand. This coordinated sequence of events ensures accurate repair and maintenance of genomic stability.
  • Evaluate the importance of base excision repair in preventing mutations and its implications for human health.
    • Base excision repair is vital for preventing mutations that could lead to significant health issues like cancer. By efficiently correcting small-scale DNA damage caused by normal cellular processes or environmental factors, this mechanism helps maintain genomic integrity. Failures in this repair pathway can lead to an accumulation of mutations over time, contributing to disease development. Understanding this repair system not only highlights its role in cellular health but also provides insights into potential therapeutic targets for diseases associated with DNA damage.
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