Which base is modified by formic acid in Maxam-Gilbert sequencing?
Maxam-Gilbert chemistry employs formic acid as a depurinating agent. Formic acid weakens the N-glycosidic bond of purines by protonation, leading to loss of adenine and guanine bases and formation of apurinic sites. Subsequent treatment with piperidine cleaves the phosphodiester backbone at those abasic positions, generating fragments ending at purines. Hence formic acid produces an A plus G specific ladder, whereas dimethyl sulfate is tuned for G alone. Pyrimidines C and T are not targeted by formic acid; hydrazine targets them instead.
Ref: NCERT Biology Class XII Principles on Klenow fill-in labeling, Lehninger Chapter 9 DNA cloning techniques, and Molecular Cloning by Sambrook Chapter 10 documenting end-labeling of cohesive termini.