Depurination decreases fidelity of dna synthesis in vitro

ABSTRACT DEPURINATION of DNA results from the breakage of the glycosidic bond between the purine base and the deoxyribose moiety of the purine nucleotides without disrupting the structural

integrity of the phosphodiester backbone. Measurements of the rates of depurination of both synthetic polynucleotides and natural DNA in various conditions _in vitro_ suggest that this

damage to DNA is a frequent cellular event1. The _in vivo_ rate constant has been estimated1 to be of the order of 1.8 × 10−9min−1. Alkylation2,3 and specific glycosidases4,5 increase the

depurination rate constants of those altered bases to 0.08–1.4 × 10−3 and 4.0 × 10−3, respectively. We have therefore been concerned with the possible consequences which may result during

replication, repair or transcription when the template contains unrepaired apurinic sites. The biological effects of depurination are not clear. Depurination of DNA has been equated with

strand breakage, a potentially lethal lesion6,7, but other evidence indicates that the apurinic site may be quite stable in cells with a half life of up to several months8,9. It is possible,

therefore, that depurination of DNA can be a mutagenic event. Mutagenesis by depurination might occur either by an insertion of an incorrect nucleotide opposite the apurinic site or by a

deletion at that point during DNA replication or repair. In view of the potentially large number of apurinic sites and their apparent stability, we investigated the effects of depurination

of DNA on the fidelity of DNA synthesis _in vitro_. Recent reports suggest that modification of polynucleotide or DNA templates by various agents, including chemical carcinogens and

ultraviolet irradiation, may affect the fidelity of DNA synthesis10–12. We report here that depurination of the synthetic polynucleotide polyd(A-T) results in a decrease in the fidelity of

DNA synthesis _in vitro_ using the DNA polymerase from avian myeloblastosis virus (AMV). This is the first demonstration of a possible relationship between depurination and mutagenesis

through incorporation of non-complementary nucleotides during DNA synthesis _in vitro_. Access through your institution Buy or subscribe This is a preview of subscription content, access via

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REPLICATION BARRIER Article 09 April 2024 BACTERIOPHAGE-RELATED EPIGENETIC NATURAL AND NON-NATURAL PYRIMIDINE NUCLEOTIDES AND THEIR INFLUENCE ON TRANSCRIPTION WITH T7 RNA POLYMERASE Article

Open access 09 November 2024 HIGH FIDELITY DNA LIGATION PREVENTS SINGLE BASE INSERTIONS IN THE YEAST GENOME Article Open access 09 October 2024 REFERENCES * Lindahl, T. & Nyberg, B.

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references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * The Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania, 19111 CLYDE W. SHEARMAN & LAWRENCE A.

LOEB Authors * CLYDE W. SHEARMAN View author publications You can also search for this author inPubMed Google Scholar * LAWRENCE A. LOEB View author publications You can also search for this

author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE SHEARMAN, C., LOEB, L. Depurination decreases fidelity of DNA synthesis

_in vitro_. _Nature_ 270, 537–538 (1977). https://doi.org/10.1038/270537a0 Download citation * Received: 08 August 1977 * Accepted: 30 October 1977 * Issue Date: 08 December 1977 * DOI:

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