A patient has Ataxia-Telangiectasia (A-T). The mutated gene ATM encodes a kinase that responds to double-strand breaks (DSBs). Which histone modification occurs immediately at DSB sites and serves as the earliest molecular marker used to detect and quantify DSBs?

• A H3K4me3 (trimethylation of histone H3 lysine 4)
• B H4K16 acetylation
• C H3K9me2 (dimethylation of H3 lysine 9)
• D H2AX phosphorylation at serine 139 (gamma-H2AX) ✓

Explanation

ATM kinase (activated by DSBs via the MRN complex) phosphorylates histone H2AX at serine 139 within minutes of DSB formation, producing gamma-H2AX foci that spread over megabase domains flanking the break. Gamma-H2AX serves as a chromatin beacon recruiting DNA repair factors (MDC1, 53BP1, BRCA1) and is the standard molecular marker for DSB quantification (detected by immunofluorescence). H3K4me3 marks active gene promoters; H3K9me2 marks heterochromatin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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