Crosstalk between replicative and translesional DNA polymerases: PDIP38 interacts directly with Poleta.
Replicative DNA polymerases duplicate genomes in a very efficient and accurate mode. However their progression can be blocked by DNA lesions since they are unable to accommodate bulky damaged bases in their active site. In response to replication blockage, monoubiquitination of PCNA promotes the switch between replicative and specialized polymerases proficient to overcome the obstacle. In this study, we characterize novel connections between proteins involved in replication and TransLesion Synthesis (TLS). We demonstrate that PDIP38 (Poldelta interacting protein of 38kDa) directly interacts with the TLS polymerase Poleta. Interestingly, the region of Poleta interacting with PDIP38 is found to be located within the ubiquitin-binding zinc finger domain (UBZ) of Poleta. We show that the depletion of PDIP38 increases the number of cells with Poleta foci in the absence of DNA damage and diminishes cell survival after UV irradiation. In addition, PDIP38 is able to interact directly not only with Poleta but also with the specialized polymerases Rev1 and Polzeta (via Rev7). We thus suggest that PDIP38 serves as a mediator protein helping TLS Pols to transiently replace replicative polymerases at damaged sites.
Tissier
Agnès
A
CNRS, UPR, Conventionné par l'Université d'Aix-Marseille, France. tissiera@lyon.fnclcc.fr
Janel-Bintz
Régine
R
Coulon
Stéphane
S
Klaile
Esther
E
Kannouche
Patricia
P
Fuchs
Robert P
RP
Cordonnier
Agnès M
AM
D002461:Cell Line, Transformed; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004261:DNA Replication / Q000235:genetics / Q000528:radiation effects; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D011485:Protein Binding; D000099270:Y-Family DNA Polymerases
D004247:DNA; D004259:DNA-Directed DNA Polymerase; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; C473592:POLDIP2 protein, human; C425929:DNA polymerase zeta; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases; C112338:Rad30 protein