Abstract
Free radical attack on the sugar-phosphate backbone generates oxidized apurinic/apyrimidinic (AP) residues in DNA. 2'-deoxyribonolactone (dL) is a C1'-oxidized AP site damage generated by UV and {gamma}-irradiation, and certain anticancer drugs. If not repaired dL produces G {yields} A transitions in Escherichia coli. In the base excision repair (BER) pathway, AP endonucleases are the major enzymes responsible for 5'-incision of the regular AP site (dR) and dL. DNA glycosylases with associated AP lyase activity can also efficiently cleave regular AP sites. Here, we report that dL is a substrate for AP endonucleases but not for DNA glycosylases/AP lyases. The kinetic parameters of the dL-incision were similar to those of the dR. DNA glycosylases such as E. coli formamidopyrimidine-DNA glycosylase, mismatch-specific uracil-DNA glycosylase, and human alkylpurine-DNA N-glycosylase bind strongly to dL without cleaving it. We show that dL cross-links with the human proteins 8-oxoguanine-DNA (hOGG1) and thymine glycol-DNA glycosylases (hNth1), and dR cross-links with Nth and hNth1. These results suggest that dL and dR induced genotoxicity might be strengthened by BER pathway in vivo.
Faure, Virginie;
[1]
Saparbaev, Murat;
[2]
Dumy, Pascal;
[1]
Constant, Jean-Francois
[1]
- LEDSS-UMR 5616, ICMG-FR 2607, BP 53, Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France)
- Group Reparation de l'ADN, UMR 8126 C.N.R.S., Institut Gustave Roussy, 39, rue Camille Desmoulins, 94805 Villejuif Cedex (France)
Citation Formats
Faure, Virginie, Saparbaev, Murat, Dumy, Pascal, and Constant, Jean-Francois.
Action of multiple base excision repair enzymes on the 2'-deoxyribonolactone.
United States: N. p.,
2005.
Web.
doi:10.1016/j.bbrc.2005.01.082.
Faure, Virginie, Saparbaev, Murat, Dumy, Pascal, & Constant, Jean-Francois.
Action of multiple base excision repair enzymes on the 2'-deoxyribonolactone.
United States.
https://doi.org/10.1016/j.bbrc.2005.01.082
Faure, Virginie, Saparbaev, Murat, Dumy, Pascal, and Constant, Jean-Francois.
2005.
"Action of multiple base excision repair enzymes on the 2'-deoxyribonolactone."
United States.
https://doi.org/10.1016/j.bbrc.2005.01.082.
@misc{etde_20619427,
title = {Action of multiple base excision repair enzymes on the 2'-deoxyribonolactone}
author = {Faure, Virginie, Saparbaev, Murat, Dumy, Pascal, and Constant, Jean-Francois}
abstractNote = {Free radical attack on the sugar-phosphate backbone generates oxidized apurinic/apyrimidinic (AP) residues in DNA. 2'-deoxyribonolactone (dL) is a C1'-oxidized AP site damage generated by UV and {gamma}-irradiation, and certain anticancer drugs. If not repaired dL produces G {yields} A transitions in Escherichia coli. In the base excision repair (BER) pathway, AP endonucleases are the major enzymes responsible for 5'-incision of the regular AP site (dR) and dL. DNA glycosylases with associated AP lyase activity can also efficiently cleave regular AP sites. Here, we report that dL is a substrate for AP endonucleases but not for DNA glycosylases/AP lyases. The kinetic parameters of the dL-incision were similar to those of the dR. DNA glycosylases such as E. coli formamidopyrimidine-DNA glycosylase, mismatch-specific uracil-DNA glycosylase, and human alkylpurine-DNA N-glycosylase bind strongly to dL without cleaving it. We show that dL cross-links with the human proteins 8-oxoguanine-DNA (hOGG1) and thymine glycol-DNA glycosylases (hNth1), and dR cross-links with Nth and hNth1. These results suggest that dL and dR induced genotoxicity might be strengthened by BER pathway in vivo.}
doi = {10.1016/j.bbrc.2005.01.082}
journal = []
issue = {4}
volume = {328}
journal type = {AC}
place = {United States}
year = {2005}
month = {Mar}
}
title = {Action of multiple base excision repair enzymes on the 2'-deoxyribonolactone}
author = {Faure, Virginie, Saparbaev, Murat, Dumy, Pascal, and Constant, Jean-Francois}
abstractNote = {Free radical attack on the sugar-phosphate backbone generates oxidized apurinic/apyrimidinic (AP) residues in DNA. 2'-deoxyribonolactone (dL) is a C1'-oxidized AP site damage generated by UV and {gamma}-irradiation, and certain anticancer drugs. If not repaired dL produces G {yields} A transitions in Escherichia coli. In the base excision repair (BER) pathway, AP endonucleases are the major enzymes responsible for 5'-incision of the regular AP site (dR) and dL. DNA glycosylases with associated AP lyase activity can also efficiently cleave regular AP sites. Here, we report that dL is a substrate for AP endonucleases but not for DNA glycosylases/AP lyases. The kinetic parameters of the dL-incision were similar to those of the dR. DNA glycosylases such as E. coli formamidopyrimidine-DNA glycosylase, mismatch-specific uracil-DNA glycosylase, and human alkylpurine-DNA N-glycosylase bind strongly to dL without cleaving it. We show that dL cross-links with the human proteins 8-oxoguanine-DNA (hOGG1) and thymine glycol-DNA glycosylases (hNth1), and dR cross-links with Nth and hNth1. These results suggest that dL and dR induced genotoxicity might be strengthened by BER pathway in vivo.}
doi = {10.1016/j.bbrc.2005.01.082}
journal = []
issue = {4}
volume = {328}
journal type = {AC}
place = {United States}
year = {2005}
month = {Mar}
}