DNA Replication and Repair Quiz

Study Notes

Distinguish between nucleotide synthesis for DNA (replication) and RNA (transcription).
Explain replication challenges of linear DNA and nuclear solutions.
Restate functions of proteins involved in DNA replication.
Identify and explain problems with telomere replication and solutions.
Discuss the limited division capacity of cells lacking telomerase.
Compare DNA damage and mutations.
Differentiate spontaneous DNA damage from chemical/radiation damage.
Illustrate repair mechanisms for deaminations, depurinations, and pyrimidine dimers.
Name repair mechanisms from descriptions or diagrams.
Associate Lynch syndrome with mismatch repair and Xeroderma Pigmentosum (XP) with nucleotide excision repair.
Describe MSH and MLH protein roles in Lynch syndrome.

Eukaryotic replication rate is approximately 50 nucleotides/second.
Having around 4000 origins of replication per genome leads to ≈8 hours for complete DNA replication.

Separation of DNA strands exposes hydrogen bond regions for base pairing.
Free nucleotides are incorporated into newly synthesized strands by DNA polymerase.
Prokaryotic DNA has three polymerases; Pol III is crucial for both leading and lagging strand synthesis and has proofreading ability.

All DNA polymerases add deoxynucleotides to the 3' hydroxyl group of a DNA chain.
Key fidelity mechanism is proofreading by eukaryotic polymerases δ and ε, which can remove mismatches.

DNA strands are antiparallel, complicating linear DNA replication.
DNA primase synthesizes short RNA primers allowing DNA polymerase to initiate DNA synthesis.

Leading strand synthesized continuously; lagging strand synthesized in segments called Okazaki fragments.
RNA primers provide a 3' hydroxyl for DNA polymerase; RNA is later replaced with DNA and sealed by ligase.

Telomeres, repeating sequences at chromosome ends, prevent chromosome shortening.
Telomerase, an enzyme with reverse transcriptase activity and RNA template, extends telomeric sequences.
Somatic cells lack telomerase, leading to gradual telomere shortening and limited cell divisions (~50 times).

DNA replication introduces 100-200 mutations per round; high fidelity is critical to reduce errors.
DNA damage is frequent occurrence; mutations arise from uncorrected damage.

Spontaneous damage includes deamination (loss of amine groups) and depurination (cleavage between purine bases and sugar).
Chemical/radiation damage, such as UV light-induced pyrimidine dimers, affect DNA structure.

Two main categories: direct reversal of damage and excision repair (removal and replacement).
Base excision repair targets specific damaged bases, utilizing DNA glycosylases and other enzymes to restore normal DNA.

Identifies and repairs incorrectly paired bases post-replication, crucial for genomic stability.
Lynch syndrome is associated with mismatch repair deficiencies, contributing to colorectal cancer.

Repairs bulky DNA adducts causing structural damage; enzymes recognize and excise damaged segments.
Xeroderma Pigmentosum results from faulty nucleotide excision repair mechanisms.