Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymerase.
The prototypic Y family DNA polymerase IV (PolIV) of Escherichia coli is involved in multiple replication-associated processes including spontaneous mutagenesis, translesion synthesis (TLS), cell fitness, survival under stressful conditions and checkpoint like functions. It interacts physically and functionally with the replisome's beta processivity clamp through the canonical PolIV C-terminal peptide (CTP). A second interaction that involves a portion of the little finger (LF) domain of PolIV has been structurally described. Here we show that the LF-beta interaction stabilizes the clamp-polymerase complex in vitro and is necessary for the access of PolIV to ongoing replication forks in vivo. However, in contrast to the CTP-beta, the LF-beta interaction is dispensable for the role of the polymerase in TLS. This discloses two independent modes of action for PolIV and, in turn, uncovers a novel way by which the cell may regulate the potentially deleterious effect of such low fidelity polymerases during replication.
CNRS FRE3211, ESBS, Université de Strasbourg, BP 10413, 67412 Strasbourg Cedex, France. j.wagner@unistra.fr
Jérôme
J
Wagner
Hélène
H
Etienne
Robert P
RP
Fuchs
Agnes
A
Cordonnier
Dominique
D
Burnouf
D004258:DNA Polymerase III / Q000378:metabolism*; D019951:DNA Polymerase beta / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D016296:Mutagenesis; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping
D004269:DNA, Bacterial; C101139:beta subunit, DNA polymerase III; D004258:DNA Polymerase III; D019951:DNA Polymerase beta