Project Details
Projekt
Biochemical Investigation on the Mechanism of Error Free Postreplication Repair (PRR) using baker yeast Saccharomyces cerevisiae as a model organism
Applicant
Dr. Christopher Ede
Subject Area
General Genetics and Functional Genome Biology
Term
from 2011 to 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 201960739
DNA lesions can result in an arrest of the replicative DNA-polymerase during replication, which would lead to cell death in case it remains unresolved. Regarding the recent doctrine, three independent processes exist to resolve replication arrests: 1. Translesion synthesis by a specialized DNA-Polymerase (TLS), 2. Error free lesion bypass by homologous recombination with the sister chromatid and 3. Error free Postreplication Repair (PRR) whose mechanisms is still unkown. Usage of these mechanisms is regulated through modification of the processivity factor PCNA: mono-ubiquitylation of lysine 164 results in translesion synthesis, poly-ubiquitylation of lysine 164 results in error free PRR. SUMOylation of lysine 164 instead represses the usage of HR. Recently, data was shown suggesting that HR yet is participating in error free PRR. Regarding this, a new model for error free PRR may be proposed including HR. This model is based upon a dual mechanism: one the one hand, lesion bypass by HR acts as an alternative, in case translesion synthesis proves impossible or inefficient. On the other hand, inefficient TLS by Pol eta may be enhanced by recruiting a second Polymerase (Pol zeta) which supports Pol eta in TLS. Based on this model, two predictions may be made: 1. Efficiency of HR may be enhanced by poly-ubiquitylated PCNA and 2. Efficiency of Pol zeta may be enhanced by poly-ubiquitylated PCNA or Pol zeta is recruited specifically to poly-ubiquitylated PCNA. Aim of the project proposed here is to test these predictions to verify the new model by using biochemical approaches.
DFG Programme
Research Fellowships
International Connection
USA
