A new method for sequencing DNA (DNA chemistry/dimethyl sulfate cleavage/hydrazine/piperidine)

DNA can be sequenced by a chemical proce- dure that breaks a terminally labeled DNA molecule partially at each repetition of a base. The lengths of the labeled fragments then identify the positions of that base. We describe reactions that cleave DNA preferentially at guanines, at adenines, at cy- tosines and thymines equally, and at cytosines alone. When the products of these four reactions are resolved by size, by elec- trophoresis on a polyacrylamide gel, the DNA sequence can be read from the pattern of radioactive bands. The technique will permit sequencing of at least 100 bases from the point of la- beling.