Skip Navigation

Publication Detail

Title: Nucleosome disruption by DNA ligase III-XRCC1 promotes efficient base excision repair.

Authors: Odell, Ian D; Barbour, Joy-El; Murphy, Drew L; Della-Maria, Julie A; Sweasy, Joann B; Tomkinson, Alan E; Wallace, Susan S; Pederson, David S

Published In Mol Cell Biol, (2011 Nov)

Abstract: Each day, approximately 20,000 oxidative lesions form in the DNA of every nucleated human cell. The base excision repair (BER) enzymes that repair these lesions must function in a chromatin milieu. We have determined that the DNA glycosylase hNTH1, apurinic endonuclease (APE), and DNA polymerase β (Pol β), which catalyze the first three steps in BER, are able to process their substrates in both 601- and 5S ribosomal DNA (rDNA)-based nucleosomes. hNTH1 formed a discrete ternary complex that was displaced by the addition of APE, suggesting an orderly handoff of substrates from one enzyme to the next. In contrast, DNA ligase IIIα-XRCC1, which completes BER, was appreciably active only at concentrations that led to nucleosome disruption. Ligase IIIα-XRCC1 was also able to bind and disrupt nucleosomes containing a single base gap and, because of this property, enhanced both its own activity and that of Pol β on nucleosome substrates. Collectively, these findings provide insights into rate-limiting steps that govern BER in chromatin and reveal a unique role for ligase IIIα-XRCC1 in enhancing the efficiency of the final two steps in the BER of lesions in nucleosomes.

PubMed ID: 21930793 Exiting the NIEHS site

MeSH Terms: Animals; DNA Damage/genetics; DNA Glycosylases/metabolism; DNA Ligase ATP; DNA Ligases/metabolism*; DNA Polymerase beta/metabolism; DNA Repair/genetics*; DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism; DNA-Binding Proteins/metabolism*; DNA/genetics; DNA/metabolism; Deoxyribonuclease (Pyrimidine Dimer)/metabolism; Humans; Lytechinus/genetics; Nucleosomes/metabolism*; Poly-ADP-Ribose Binding Proteins; Reactive Oxygen Species; X-ray Repair Cross Complementing Protein 1; Xenopus Proteins; Xenopus/genetics

Back
to Top