16 Questions
Which category of DNA damage is caused by factors within the body?
Spontaneous (endogenous)
What is the main implication of DNA being constantly damaged and accumulating damage over its lifetime?
It can lead to genetic instability
According to Errol Friedberg's review, what does life require in relation to DNA damage and genetic stability?
Balance between avoidance of mutations and generation of mutations
What are the phenotypic consequences of the generation and persistence of mutations according to Errol Friedberg's review?
Development of cancer
In reality, what is the only molecule that relies solely on repair of existing molecules?
DNA
What did Errol Friedberg emphasize in his 2001 review regarding DNA damage and genetic stability?
Balancing avoidance of mutations and generation of mutations
Which category of DNA damage arises during DNA replication, DNA repair, and DNA rearrangement?
Spontaneous (endogenous)
What contributes more to the damage of DNA, spontaneous or environmental category?
Spontaneous (endogenous)
Which chemical mutagen is an example of an alkylating agent?
Polycyclic aromatic hydrocarbons
What is the impact of the Aspartic acid to alanine change at residue 400 in the proofreading domain of DNA polymerase delta?
Higher susceptibility to malignancies
What is the function of mismatch repair proteins in DNA replication?
Recognize and repair base misincorporation errors
What is the error frequency for one cycle of replication without proofreading by DNA polymerases?
$1$ in $10^5$ copied nucleotides
How many double strand breaks are estimated to be formed per cell during S-phase?
$10$
What is the functional equivalence of a single strand break during replication?
DNA double strand break
What can DNA polymerases including polymerase delta do when copying repeated sequences of DNA in the template strand?
"Stutter" or skip a base
What is the impact of 3’ to 5’ proofreading by polymerases during replication?
Reduction of error frequency to $1$ in $10^9$ copied nucleotides
Study Notes
DNA Damage and Genetic Stability
- Endogenous DNA damage, which is caused by factors within the body, occurs constantly and accumulates over time.
- The constant damage and accumulation of mutations can lead to phenotypic consequences, such as changes in the characteristics of an organism.
Importance of DNA Repair and Genetic Stability
- Life requires a balance between DNA damage and genetic stability, as emphasized by Errol Friedberg in his 2001 review.
- DNA is the only molecule that relies solely on the repair of existing molecules.
Categories of DNA Damage
- Genetic instability can arise from endogenous DNA damage, which occurs within the body.
- Exogenous DNA damage, which is caused by environmental factors, contributes more to the overall damage of DNA.
- A third category of DNA damage, operational errors, arises during DNA replication, DNA repair, and DNA rearrangement.
Chemical Mutagens and DNA Damage
- Alkylating agents, such as ethyl methanesulfonate, are a type of chemical mutagen that can cause DNA damage.
DNA Polymerase and Proofreading
- The Aspartic acid to alanine change at residue 400 in the proofreading domain of DNA polymerase delta reduces its proofreading activity.
- Mismatch repair proteins function to correct errors in DNA replication.
- Without proofreading, the error frequency for one cycle of DNA replication is approximately 10^-5.
- DNA polymerases, including polymerase delta, can slip or stutter when copying repeated sequences of DNA in the template strand, leading to errors.
- The 3’ to 5’ proofreading activity of polymerases during replication reduces error rates.
DNA Replication and Breaks
- An estimated 10-20 double-strand breaks are formed per cell during the S-phase of DNA replication.
- A single-strand break during replication is functionally equivalent to a double-strand break.
This quiz covers the topic of spontaneous DNA damage, distinguishing between the two main categories of DNA damage and understanding the main types and causes of spontaneous damage to DNA.
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