Pivotal role of the beta-clamp in translesion DNA synthesis and mutagenesis in E. coli cells.
The genetic information is continuously subjected to the attack by endogenous and exogenous chemical and physical carcinogens that damage the DNA template, thus compromising its biochemical functions. Despite the multiple and efficient DNA repair systems that have evolved to cope with the large variety of damages, some lesions may persist and, as a consequence, interfere with DNA replication. By essence, the damaged-DNA replication process (hereafter termed translesion synthesis or TLS) is a major source of point mutations and is therefore deeply involved in the onset of human diseases such as cancer. Recent identification of numerous DNA polymerases involved in TLS has shed new light onto the molecular mechanisms of mutagenesis. Here, we show that in vivo, both error-free and mutagenic bypass activities of the three DNA polymerases known to be involved in TLS in Escherichia coli (PolII, PolIV and PolV) strictly depend upon the integrity of small peptidic sequences identified as their beta-clamp binding motif. Thus, in addition to its crucial role as the processivity factor of the PolIII replicase, the beta-clamp plays a pivotal role during the TLS process.
Becherel
Olivier J
OJ
Institut de Recherche contre les Cancers de l'Appareil Digestif, Unité Propre de Recherche 9003 du Centre National de la Recherche Scientifique, Hôpitaux Universitaires BP424, UPR conventionnée de l'Université Louis Pasteur de Strasbourg, France.
Fuchs
Robert P P
RP
Wagner
Jérôme
J
D004249:DNA Damage; D004257:DNA Polymerase II / Q000502:physiology*; D019951:DNA Polymerase beta / Q000502:physiology*; D004260:DNA Repair; D004261:DNA Replication / Q000502:physiology; D004269:DNA, Bacterial / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000502:physiology*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins; D016296:Mutagenesis; D009154:Mutation; D021122:Protein Subunits
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D021122:Protein Subunits; D004257:DNA Polymerase II; D019951:DNA Polymerase beta; C120926:DNA polymerase V, E coli; D004259:DNA-Directed DNA Polymerase