Which of the following describes the main mechanism of double-strand break repair in the resting phase and G1?

Options:
explanation: This describes homologous recombination (HR), a high-fidelity method of repairing double-stranded breaks. HR requires a sister chromatid to pair with, meaning it can only occur during S and G2 phases. This method is more common in prokaryotes with smaller genomes due to less complex DNA folding which makes it easier to align homologous sequences.
name: Free ends of DNA are degraded by exonucleases to make 3' overhangs, stabilised by nucleoprotein filaments which mediate invasion into the homologous sequence on the sister chromatid. The 3' overhangs are then extended by DNA polymerisation using the sister chromatid template to form a holiday junction which is cleaved, separating the chromatids
label: b
answer: no
explanation: This describes the base excision repair (BER) method of repairing single-stranded DNA damage. Mutations in proteins involved in BER have been associated with cancers. For example, OGG1 (a glycosidase) variants have been associated with breast cancers, lung cancers, renal cell carcinoma and leukaemias.
name: Damaged bases are flipped out: the bases are removed by a DNA glycosidase while the deoxyribose-phosphate backbone is left to be cleaved by an apyramidic or apurinic endonuclease. The break is recognised by DNA polymerase B which removes nucleotides in its way, replacing them until dissociating, after which a ligase re-joins the strands
label: c
answer: no
explanation: This describes non-homologous end-joining (NHEJ), a low-fidelity method of repairing double-stranded breaks. NHEJ does not require pairing with a sister chromatid, allowing it to occur at any phase. This method is more common in eukaryotes with large genomes due to the complex folding of chromatin making it more difficult to align homologous sequences.
name: Free ends of DNA are recognised by proteins such as Ku70/80 and phosphorylated by DNA-PKcs. This recruits nuclease complexes which cleave down the ends before ligation by DNA ligase 4
label: a
answer: yes
explanation: This describes the mismatch repair (MMR) method of repairing single-stranded DNA damage. Mutations in proteins involved in MMR such as MSH2, MLH1 and MSH6 can cause Lynch syndrome (also known as hereditary non-polyposis colorectal cancer - HNPCC), an autosomal dominant condition characterised by DNA microsatellite instability and increased risk of cancers, particularly colorectal cancer.

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name: Mismatched bases are flipped out, and then recognised and extruded into a loop. The daughter strand is cleaved by an endonuclease and exonuclease and is then replaced by polymerase delta/eta. A ligase re-joins the strands
label: e
answer: no
explanation: This describes the nucleotide excision repair (NER) method of repairing single-stranded DNA damage. Mutations in proteins involved in NER such as XPB, XPD and XPF can cause xeroderma pigmentosum, an autosomal recessive condition characterised by a thousand times increased incidence of tumours associated with UV light sensitivity. This is because cyclo-pyrimidine dimers generated by UV light are not repaired, causing the rapid mutation of exposed skin cells.
name: Damaged bases are flipped out: the DNA is unwound by the assembly of a TF2H holoenzyme, and then a wide margin of nucleotides are excised and replaced by polymerase delta/eta. A ligase then re-joins the strands
label: d
answer: no

Correct answer: a