About the project

New players involved in the maintenance of genomic stability

project leader Prof. Iwona J. Fijalkowska

 

The mechanisms by which cells produce, or try to avoid mutations, are of significant research interest. Important sources of mutations are replication errors. Understanding all these mechanisms and finding new factors that are responsible for accurate DNA replication has become a major challenge of current molecular biology. This knowledge should help us to understand the process of evolution, genesis of cancer, genetic disorders or aging. While the fidelity of individual DNA polymerases, including their base insertion fidelity and proofreading ability, has been investigated in detail, recent emphasis has shifted to the fidelity of chromosomal multisubunit complexes (replisomes) that perform the simultaneous replication of leading and lagging strands. Specific issues of interest are the contribution of the various noncatalytic replisomal subunits and the mechanisms underlying the involvement of the supplementary DNA polymerases that have been discovered in the recent years. Interestingly, most of the prokaryotic and eukaryotic replicative polymerases have multi-subunit structure. There are several examples indicating that not only the catalytic subunits, but also the noncatalytic subunits of DNA polymerases may function as fidelity factors during replication process.

Project aims will focus on investigation and further characterization of new factors which influence the stability of DNA. We believe that the proposed investigations will broaden the understanding of the processes that maintain stable replication forks, and provide additional knowledge about new factors influencing genomic stability.In many cases, bacteria and yeasts have been successfully used to create models for human DNA replication or human diseases. Thus, in the planned experiments Saccharomyces cerevisiae and Escherichia coli will serve as the model organisms. The experiments will be carried out in collaborations with three international laboratories: California Institute of Technology, Pasadena, CA, USA; National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; National Institute of Genetics, Mishima, Japan. Their expertise and ongoing collaboration will support our studies.

The project will focus on:

  1. Role of GINS complex in proper functioning of replication apparatus;
  2. Role of Dpb2, a noncatalytic subunit of DNA Polymerase epsilon, in genome stability;
  3. DNA polymerase switching during high fidelity or potentially error prone replication.

We are seeking highly motivated and talented young scientists for the following positions:

Please find the recruitment application form for appropriate fellowship you are applying for.