3- cancer genome stability Flashcards
What are the two main sources of DNA damage, and how many incidences of damage per cell per day can result from these sources?
The two sources of DNA damage are endogenous (internal) and exogenous (external). Together, they can result in as many as 1 million incidences of damage per cell per day.
Name three single-strand repair mechanisms and briefly describe each.
Nucleotide Excision Repair (NER): Repairs damage caused by, for example, UV light, by cutting out damaged nucleotides and replacing them.
Base Excision Repair (BER): Recognizes and removes damaged bases, such as those caused by nitrates, and fills the gap with new nucleotides.
Mismatch Repair (MMR): Corrects errors in DNA replication and recombination by recognizing mispaired nucleotides.
Describe the process of Nucleotide Excision Repair (NER) and provide an example of a condition related to its failure.
NER involves the recognition of pyrimidine dimers caused by UV light, excision of damaged nucleotides, replacement by DNA polymerase, and sealing by DNA ligase. Failure of NER can lead to conditions like melanoma when UV light-induced damage is not properly repaired.
Explain the Base Excision Repair (BER) process and provide an example of a situation where BER is needed.
: BER involves recognizing and removing damaged bases, filling the gap with new nucleotides, and sealing the gap. For instance, BER is needed when nitrates cause deamination of a base in the DNA strand.
What is the significance of Mismatch Repair (MMR), and how does it function in bacteria?
MMR corrects errors in DNA replication and recombination. In bacteria, transient methylation distinguishes the newly-synthesized daughter strand with errors from the correct parental strand, ensuring repair occurs according to the correct template.
Name three double-strand repair mechanisms and briefly describe each.
Non-homologous End Joining (NHEJ): Links broken DNA strands directly, allowing for error-prone repairs.
Microhomology-Mediated End Joining: Aligns strands based on homologous sequences and repairs using complementary base pairs.
Homologous Recombination: Requires identical or nearly identical sequences as templates for repairing double-strand breaks.
Describe the process of Non-homologous End Joining (NHEJ) in repairing double-strand breaks.
NHEJ involves a specialized DNA ligase forming a complex with a cofactor that directly joins the two ends, leading to direct ligation without the need for a homologous template.
What is the role of Homologous Recombination in repairing double-strand breaks, and what templates are used?
Homologous Recombination requires identical or nearly identical sequences as templates for repairing breaks. It allows damaged chromosomes to be repaired using a sister chromatid or a homologous chromosome as a template.
Provide examples of endogenous and exogenous sources of DNA damage.
Endogenous Sources: DNA replication errors, alkylation, hydrolysis, reactive oxygen species (ROS).
Exogenous Sources: UV from the sun, X-rays, gamma rays, environmental chemicals, viruses, chemotherapy for cancer treatment.
