Biomaterial Database

Mechanism of DNA strand breakage by piperidine at sites of N7-alkylguanines. 1986

W B Mattes, and J A Hartley, and K W Kohn

The volatile, secondary amine piperidine is used in the Maxam-Gilbert chemical method of DNA sequencing to create strand breaks in DNA at sites of damaged bases. As such it is often used in generalized studies of DNA damage to identify 'alkali-labile lesions'. We confirm the mechanism proposed by Maxam and Gilbert (Maxam, A. and Gilbert, W. (1980) Methods Enzymol. 65, 499-560) by which aqueous piperidine creates strand breaks at sites of N7-guanine alkylations: alkaline conditions catalyze rupture of the C8-N9 bond, forming a formamido-pyrimidine structure which is displaced from the ribose moiety by piperidine. In keeping with this mechanism, the tertiary amine, N-methylpiperidine, does not catalyze the formation of strand breaks in alkylated DNA. Our data confirm the prediction that high pH in and of itself will not create strand breaks at sites of N7-alkylguanines.

UI	MeSH Term	Description	Entries
D010880	Piperidines	A family of hexahydropyridines.
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004591	Electrophoresis, Polyacrylamide Gel	Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.	Polyacrylamide Gel Electrophoresis,SDS-PAGE,Sodium Dodecyl Sulfate-PAGE,Gel Electrophoresis, Polyacrylamide,SDS PAGE,Sodium Dodecyl Sulfate PAGE,Sodium Dodecyl Sulfate-PAGEs
D006147	Guanine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000478	Alkylation	The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group.	Alkylations