DNA Repair Mechanisms

What DNA repair pathway is defective in Lynch syndrome?

Mismatch repair (MMR).

What is another name for Lynch syndrome?

Hereditary nonpolyposis colorectal cancer (HNPCC).

What does mismatch repair (MMR) fix?

Incorrectly paired DNA bases after replication.

What proteins are involved in bacterial mismatch repair?

MutS, MutL, and MutH.

How does bacterial mismatch repair distinguish old from new DNA?

Hemimethylation: the older strand is methylated, while the newly synthesized strand is not yet methylated.

When does mismatch repair occur?

After DNA replication, during late S phase and G2.

What DNA repair pathway is defective in xeroderma pigmentosum (XP)?

Nucleotide excision repair (NER).

What type of DNA damage is repaired by nucleotide excision repair (NER)?

Bulky, helix-distorting DNA lesions, especially UV-induced pyrimidine (thymine) dimers.

What causes thymine dimers?

UV radiation causes adjacent thymine bases to form abnormal covalent bonds.

What bacterial proteins are involved in nucleotide excision repair?

UvrA, UvrB, UvrC, and UvrD (UvrABCD).

How does nucleotide excision repair (NER) work?

Recognizes a bulky lesion, removes a short DNA segment surrounding it, then DNA polymerase fills the gap and ligase seals it.

What is the classic clinical clue for xeroderma pigmentosum?

Extreme UV sensitivity due to defective repair of UV-induced DNA damage.

What does base excision repair (BER) fix?

Individual damaged bases, including deaminated or alkylated bases, and AP sites.

What is the enzyme sequence in base excision repair?

DNA glycosylase → AP endonuclease → DNA polymerase.

What does DNA glycosylase do in BER?

Removes a damaged base by cleaving its N-glycosidic bond, producing an AP site.

What does AP endonuclease do in BER?

Cuts the DNA backbone at an AP site so the damaged region can be replaced.

What clinical condition is associated with alkyladenine DNA glycosylase overexpression in Lecture 11?

Ulcerative colitis; this is an association, not a stated cause of the disease.

Which DNA repair pathway requires BRCA1 and BRCA2?

Homologous recombination (HR).

What diseases are associated with defective homologous recombination involving BRCA1/BRCA2?

Breast and ovarian cancers.

What DNA damage does homologous recombination repair?

Double-strand DNA breaks using homologous DNA as a repair template, especially in S phase.

What does nonhomologous end joining (NHEJ) repair?

Double-strand DNA breaks without using a homologous template.

Why is nonhomologous end joining error-prone?

It directly reconnects broken DNA ends and can produce insertions or deletions.

What immune function is associated with nonhomologous end joining?

Generation of immunoglobulin and T-cell receptor diversity.

What is translesion synthesis (TLS)?

An error-prone DNA damage-bypass process that allows replication to continue past lesions without removing them.

Which polymerase and disease are associated with translesion synthesis defects?

DNA polymerase eta (η) and xeroderma pigmentosum variant (XP-V). Lecture 11 also mentions SCID in relation to TLS defects.

Aminoglycosides + Tetracyclins bind to

bind to 30s ribsomal subunit

Macrolides + Cloramphenicol

bind to 50s ribosomal subunit.

Prokaryotes have # RNA Polymerases

1

Eukaryotes have # RNA Polymerases

3