Recognition and kinetics for excision of a base lesion within clustered DNA damage by the Escherichia coli proteins Fpg and Nth

Biochemistry
M H David-CordonnierPeter O'Neill

Abstract

Ionizing radiation and radiomimetic anticancer agents induce clustered DNA damages that are thought to lead to deleterious biological consequences, due to the challenge that clustered damage may present to the repair machinery of the cell. Specific oligonucleotides, containing either dihydrothymine (DHT) or 7,8-dihydro-8-oxoguanine (8-oxoG) opposite to specific lesions at defined positions on the complementary strand, have been used to determine the kinetic constants, K(M), k(cat), and specificity constants, for excision of DHT and 8-oxoG by the Escherichia coli base excision repair proteins, endonuclease III (Nth) and formamidopyrimidine glycosylase (Fpg), respectively. For excision of DHT opposite to 8-oxoadenine by Nth or Fpg proteins, or 8-oxoG opposite to 8-oxoG by Fpg, the major change in the specificity constant occurs when the second lesion on the complementary strand is one base to the site opposite to DHT or 8-oxoG. The specificity constants for excision of DHT or 8-oxoG by both proteins are reduced by up to 2 orders of magnitude when an abasic site or a strand break is opposite on the complementary strand. Whereas the values of K(M) are only slightly affected by the presence of a second lesion, the major change is se...Continue Reading

References

Jan 1, 1994·Annual Review of Biochemistry·B Demple, L Harrison
Jun 29, 1999·Radiation and Environmental Biophysics·H NikjooD T Goodhead
Jul 9, 1999·Journal of Molecular Biology·L HarrisonS S Wallace
Apr 15, 2000·The Journal of Biological Chemistry·M H David-CordonnierP O'Neill

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Citations

Nov 26, 2003·Mutation Research·Jean CadetJean-Luc Ravanat
Feb 10, 2004·Protein Expression and Purification·Prasad ReddyMiral Dizdaroglu
Jun 1, 2002·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Lynn Harrison, Svitlana Malyarchuk
Feb 13, 2003·Nucleic Acids Research·Ann-Karin OlsenGunnar Brunborg
Jul 31, 2003·Nucleic Acids Research·Dwain I D'souza, Lynn Harrison
Oct 19, 2006·Radiation and Environmental Biophysics·Didier BoucherDietrich Averbeck
Apr 5, 2005·Journal of Computational Chemistry·Hirofumi FujimotoHideaki Maekawa
Jun 28, 2005·DNA Repair·Markus Löbrich, Penny A Jeggo
Dec 7, 2010·Mutation Research·Laura J EcclesMartine E Lomax
Nov 3, 2016·International Journal of Radiation Biology·Iyo ShiraishiAkinari Yokoya
Jul 24, 2008·Dose-response : a Publication of International Hormesis Society·Daniel P Hayes
Mar 31, 2015·Nucleic Acids Research·Pamela ReynoldsPeter O'Neill
Dec 17, 2002·Oncogene·Bruce Demple, Michael S DeMott
Apr 1, 2021·International Journal of Radiation Biology·Susan S Wallace

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