PMID: 6403037Apr 15, 1983Paper

Structure of repaired sites in human DNA synthesized in the presence of inhibitors of DNA polymerases alpha and beta in human fibroblasts

Biochimica Et Biophysica Acta
J E Cleaver

Abstract

Excision repair of ultraviolet damage in human fibroblasts was partially inhibited by drugs that block DNA polymerases alpha or beta (cytosine arabinoside, aphidicolin and dideoxythymidine) causing a reduction in unscheduled synthesis and an accumulation of single-strand breaks. The strand breaks accumulated in the presence of aphidicolin could be resealed within 30 min after removal of the drug, but those accumulated by cytosine arabinoside took many hours. Digestion of repaired DNA with exonuclease III or S1 nuclease revealed that even the highest concentration of polymerase inhibitors, singly or in combination, that produced maximal accumulation of single-strand breaks only blocked 37-86% of repair sites. Use of single-strand break frequencies to measure the number of repair events can therefore be in error by as much as a factor of 3. The blocked patches with free 3'OH termini were, on average, 22% of normal length, corresponding to between 6 and 17 bases (assuming a normal patch of 25-75 bases in length). Patches that remained unsealed in vivo were also resistant to sealing by T4 ligase in vitro. The data are more consistent with a mechanism of repair in which long single-strand gaps are first made by excision enzymes and ...Continue Reading

References

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Citations

Jun 1, 1989·Mutation Research·D SmeetsT Hustinx
Jan 1, 1990·Pharmacology & Therapeutics·R V Talanian, G E Wright
May 1, 1986·Mutation Research·J P Th'ng, I G Walker
Sep 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·D L BusbeeP W Rankin
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·O W McBrideS H Wilson
Oct 11, 1990·Nucleic Acids Research·T OhnishiA Matsukage
Sep 1, 1990·Photochemistry and Photobiology·R D Snyder, P S Sunkara
Nov 15, 1985·Biochemical and Biophysical Research Communications·F LicastroR L Walford
Nov 1, 1985·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·R M TyrrellM Pidoux
Feb 1, 1989·Molecular and Cellular Biology·A J FornaceS H Wilson
Feb 28, 1988·Biochimica Et Biophysica Acta·S WilsonS Widen
Jan 6, 1992·Biochimica Et Biophysica Acta·O Popanda, H W Thielmann
Nov 15, 1989·Biochemical and Biophysical Research Communications·I S ParkS D Park

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