In CRISPR-Cas9 gene editing, Cas9 creates a double-strand break (DSB) in DNA at a site determined by the guide RNA (gRNA). The two primary pathways for DSB repair differ in their outcomes. Which pathway is preferred for precise gene correction and requires a template?

• A Non-homologous end joining (NHEJ) — error-prone, inserts/deletions (indels) — preferred for gene correction
• B Base excision repair (BER) — precise, used for all CRISPR edits
• C Homology-directed repair (HDR) — precise, template-dependent — preferred for gene correction but active mainly in S/G2 phase ✓
• D Mismatch repair (MMR) — template-dependent, active in all cell cycle phases

Explanation

CRISPR-Cas9 creates a blunt-ended DSB. NHEJ (non-homologous end joining) is the predominant repair pathway in mammalian cells, active in all cell cycle phases; it is error-prone, causing indels that often disrupt gene function (useful for gene knockout). HDR (homology-directed repair) requires a homologous template (donor DNA provided along with the CRISPR machinery) and is active mainly in late S/G2 phase when sister chromatids are available; it can achieve precise substitutions or insertions. For therapeutic gene correction, HDR is preferred but is less efficient; current strategies include using base editors (CBE/ABE) or prime editing to achieve precise single-base changes without DSBs.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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