Cel DNA replication is a crucial, but potentially dangerous process in every cellular division. A failure to maintain the integrity of replicating chromosomes leads to genome instability, an early event in tumorigenesis. Most common anti-cancer drugs also interfere with DNA synthesis, by largely undefined mechanisms. My lab specializes in the structural and molecular characterization of DNA replication stress in higher eukaryotes, combining standard cell and molecular biology with specialized single molecule analysis of replication intermediates.The first aim of our research is to gain mechanistic information about the elusive impact of oncogene activation on DNA replication. By direct structural analysis of tissue culture models of tumorigenesis, we have recently uncovered specific defects in DNA synthesis associated with DNA damage checkpoint activation. We plan to expand these studies to compare the effect of different oncogenes and to identify cellular factors modulating oncogene-induced genotoxicity.We are also elucidating the cytotoxic mechanisms of anti-cancer drugs that challenge DNA replication. Comparing the molecular consequences of chemotherapeutic treatments in control cells and cells lacking cancer-related factors, we plan to uncover how precisely different drugs interfere with replication and which cellular players mediate their cytotoxicity. We plan to complement these studies with a proteomic-based screen, to identify novel factors modulating replication of a damaged template.Finally, we plan to analyze replication features in different populations of stem cells, as the cellular response to replication stress was recently proven essential for stem cell maintenance. We aim to provide mechanistic insight into the constitutive activation of the DNA damage response reported in embryonic stem cells. We also plan to expand these investigations to hematopoietic stem cells, where we recently observed similar phenomena upon stimuli-induced proliferation. Dziedzina nauki natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesmolecular biology Program(-y) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) ERC-CG-2013-LS1 - ERC Consolidator Grant - Molecular and Structural Biology and Biochemistry Zaproszenie do składania wniosków ERC-2013-CoG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-CG - ERC Consolidator Grants Instytucja przyjmująca University of Zurich Wkład UE € 1 846 500,00 Adres RAMISTRASSE 71 8006 ZURICH Szwajcaria Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Massimo Lopes (Prof.) Kierownik naukowy Massimo Lopes (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko University of Zurich Szwajcaria Wkład UE € 1 846 500,00 Adres RAMISTRASSE 71 8006 ZURICH Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Massimo Lopes (Prof.) Kierownik naukowy Massimo Lopes (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych