title: The nucleoid-associated protein HU enhances 8-oxoguanine base excision by the formamidopyrimidine-DNA glycosylase.
abstract: The nucleoid-associated protein HU is involved in numerous DNA transactions and thus is essential in DNA maintenance and bacterial survival. The high affinity of HU for SSBs (single-strand breaks) has suggested its involvement in DNA protection, repair and recombination. SSB-containing DNA are major intermediates transiently generated by bifunctional DNA N-glycosylases that initiate the BER (base excision repair) pathway. Enzyme kinetics and DNA-binding experiments demonstrate that HU enhances the 8-oxoguanine-DNA glycosylase activity of Fpg (formamidopyrimidine-DNA glycosylase) by facilitating the release of the enzyme from its final DNA product (one nucleoside gap). We propose that the displacement of Fpg from its end-DNA product by HU is an active mechanism in which HU recognizes the product when it is still bound by Fpg. Through DNA binding, the two proteins interplay to form a transient ternary complex Fpg/DNA/HU which results in the release of Fpg and the molecular entrapment of SSBs by HU. These results support the involvement of HU in BER in vivo.
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France Graduate School of "Santé, Sciences Biologiques et Chimie du Vivant" (ED 549), University of Orléans, Orléans, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Le Meur
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Culard
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Nadan
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Goffinont
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Coste
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Guerin
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Loth
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Landon
authors.affiliation: Centre de Biophysique Moléculaire (UPR4301), CNRS, rue Charles Sadron, 45 071 Orléans cedex 02, France castaing@cnrs-orleans.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Castaing
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043382:DNA-Formamidopyrimidine Glycosylase / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C116822:hns protein, E coli; C024829:8-hydroxyguanine; D006147:Guanine; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli
keywords: DNA repair stimulation; Fpg (MutM); base excision repair (BER); nucleoid-associated protein (NAP) HU; single-strand break (SSB)