Jiricny, Josef - Eidgenössische Technische Hochschule Zürich - Department of Chemistry and Applied Biosciences

个人简介

Josef Jiricny joined the ETH on the 1st October 2003, as the Bonizzi-Theler Professor of Functional Genomics. He is also a full professor at the University of Zurich, having joined the faculty of medicine on the 1st August 1996, and the faculty of science on the 1st October 1999. Josef Jiricny was born in Prague on the 30th April 1951. In the summer of 1969 he emigrated to England, where he studied chemistry at the University of Aston in Birmingham. He obtained his PhD at the University of London. His first postdoctoral stage, at King's College, London, was devoted to the development of novel protecting groups for DNA synthesis. During his second postdoctoral stage at the Imperial Cancer Research Fund laboratories in London, he began to study the mechanisms of DNA repair. In 1983 he transferred his research to the Friedrich Miescher Institute in Basel, where he became a senior group leader in 1989. One year later he accepted the position of a senior director of biochemistry at the newly-founded Istituto di Richerche di Biologia Molecolare (IRBM) near Rome, where he continued to study DNA repair mechanisms, as well as coordinating research programs aimed at the discovery of novel antiviral substances. In August 1996 he moved to Zurich as director of the Institute of Molecular Cancer Research (formerly the Institute of Medical Radiobiology) of the medical faculty of the University of Zurich. Josef Jiricny studies the mechanisms of DNA mismatch repair in human cells. His research is currently focusing on the identification of the remaining components of this system and on its reconstitution from purified recombinant proteins. In parallel, he is studying the link between mismatch repair malfunction and colon cancer. He was elected to EMBO in 1996 and is a member of the editorial board of the EMBO Journal, EMBO Reports and Chemistry and Biology. He also acts on several advisory boards and is currently chairman of the steering committee of the Functional Genomics Center Zurich.

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DNA mismatch repair and colon cancer Marra, Giancarlo and Jiricny, Josef (2005) A DNA glycosylase from Pyrobaculum aerophilum with an 8-oxoguanine binding mode and a noncanonical helix-hairpin-helix structure Lingaraju, Gondichatnahalli M., Sartori, Alessandro A., Kostrewa, Dirk, Prota, Andrea E., Jiricny, Josef and Winkler, Fritz K. (2005) Studies of DNA base excision repair (BER) pathways in the hyperthermophilic crenarchaeon Pyrobaculum aerophilum identified an 8-oxoguanine-DNA glycosylase, Pa-AGOG (archaeal GO glycosylase), with distinct functional characteristics. Here, we describe its crystal structure... Characterization of the "Mismatch Repairosome" and Its Role in the Processing of Modified Nucleosides In Vitro Baerenfaller, Katja, Fischer, Franziska and Jiricny, Josef (2006) The process of postreplicative mismatch repair (MMR) increases the fidelity of DNA replication by eliminating biosynthetic errors from newly synthesized DNA. In addition, MMR proteins are also involved in the processing of intermediates of mitotic and meiotic recombination... Characterization of the "Mismatch Repairosome" and Its Role in the Processing of Modified Nucleosides In Vitro Baerenfaller, Katja, Fischer, Franziska and Jiricny, Josef (2006) The process of postreplicative mismatch repair (MMR) increases the fidelity of DNA replication by eliminating biosynthetic errors from newly synthesized DNA. In addition, MMR proteins are also involved in the processing of intermediates of mitotic and meiotic recombination... Characterization of the 'Mismatch Repairosome' and Its Role in the Processing of Modified Nucleosides In Vitro Baerenfaller, Katja, Fisher, Franziska and Jiricny, Josef (2006) The process of postreplicative mismatch repair (MMR) increases the fidelity of DNA replication by eliminating biosynthetic errors from newly synthesized DNA. In addition, MMR proteins are also involved in the processing of intermediates of mitotic and meiotic recombination... The multifaceted mismatch repair system Jiricny, Josef (2006) By removing biosynthetic errors from newly synthesized DNA, mismatch repair (MMR) improves the fidelity of DNA replication by several orders of magnitude. Loss of MMR brings about a mutator phenotype, which causes a predisposition to cancer. But MMR status also affects... MutLα: the cutting edge of eukaryotic mismatch repair Jiricny, Josef (2006) The mismatch repair process corrects errors in newly synthesized DNA. In this issue, Modrich and colleagues (Kadyrov et al., 2006) show that a component of the human mismatch repair machinery, MutLα, has endonuclease activity. MutLα introduces single-strand breaks near... MutL alpha Jiricny, Josef (2006) Transcriptome Profile of Human Colorectal Adenomas Sabates-Bellver, Jacob, Van der Flier, Laurens G., Palo, Mariagrazia de, Cattaneo, Elisa, Maake, Caroline, Rehrauer, Hubert, Laczko, Endre, Kurowski, Michal A., Bujnicki, Janusz M., Menigatti, Mirco, Luz, Judith, Ranalli, Teresa V., Gomes, Vito, Pastorelli, Alfredo, Faggiani, Roberto, Anti, Marcello, Jiricny, Josef, Clevers, Hans and Marra, Giancarlo (2007) Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their... 5-fluorouracil is efficiently removed from DNA by the base excision and mismatch repair systems Fischer, Franziska, Baerenfaller, Katja and Jiricny, Josef (2007) Background & Aims: 5-Fluorouracil (FU) is one of the mainstays of colon cancer chemotherapy. Although developed as an inhibitor of thymidylate synthase, its cytotoxicity has been linked also to its incorporation into RNA. Surprisingly, although FU is incorporated also... Mismatch repair-dependent processing of methylation damage gives rise to persistent single-stranded gaps in newly replicated DNA Mojas, Nina, Lopes, Massimo and Jiricny, Josef (2007) O6-Methylguanine (MeG) is a highly cytotoxic DNA modification generated by SN1-type methylating agents. Despite numerous studies implicating DNA replication, mismatch repair (MMR), and homologous recombination (HR) in MeG toxicity, its mode of action has remained elusive.... Background mutation frequency in microsatellite-unstable colorectal cancer Sammalkorpi, Heli, Alhopuro, Pia, Lehtonen, Rainer, Tuimala, Jarno, Mecklin, Jukka-Pekka, Järvinen, Heikki J., Jiricny, Josef, Karhu, Auli and Aaltonen, Lauri A. (2007) Microsatellite instability (MSI) is observed in similar to 12% of colorectal cancers. Genes containing a mommucleotide microsatellite in the coding sequence are particularly prone to inactivation in MSI tumorigenesis, and much work has been conducted to identify genes... Mismatch repair status and the response of human cells to cisplatin Pani, Elisabetta, Stojic, Lovorka, El-Shemerly, Mahmoud, Jiricny, Josef and Ferrari, Stefano (2007) The emergence of resistance to cisplatin is a serious drawback of cancer therapy. To help elucidate the molecular basis of this resistance, we examined matched ovarian cancer cell lines that differ in their DNA mismatch repair (MMR) status and the response to cisplatin.... Characterization of the interactome of the human MutL homologues MLH1, PMS1, and PMS2 Cannavo, Elda, Gerrits, Bertran, Marra, Giancarlo, Schlapbach, Ralph and Jiricny, Josef (2007) Postreplicative mismatch repair (MMR) involves the concerted action of at least 20 polypeptides. Although the minimal human MMR system has recently been reconstituted in vitro, genetic evidence from different eukaryotic organisms suggests that some steps of the MMR process may be... Characterisation of the mycobacterial NER system reveals novel functions of uvrD1 helicase Güthlein, Carolin, Wanner, Roger M., Sander, Peter, Davis, Elaine O., Bosshard, Martin, Jiricny, Josef, Böttger, Erik C. and Springer, Burkhard (2008) In this study, we investigated the role of the nucleotide excision repair (NER) pathway in mycobacterial DNA repair. Mycobacterium smegmatis lacking the NER excinuclease component uvrB or the helicase uvrD1 gene and a double knockout lacking both genes were constructed, and their... DNA Cytosine Demethylation Jiricny, Josef and Menigatti, Mirco (2008) Whether 5-methylcytosine (meC) can be enzymatically removed from vertebrate DNA has been the subject of extensive study and also some controversy. Rai et al. (2008) now report that cytosine demethylation can be accomplished in a one-cell zebrafish embryo by the combined... Multiplex SNaPshot Genotyping for Detecting Loss of Heterozygosity in the Mismatch-Repair Genes MLH1 and MSH2 in Microsatellite-Unstable Tumors Bujalkova, Maria, Zavodna, Katarina, Krivulcik, Tomas, Ilencikova, Denisa, Wolf, Brigitte, Kovac, Michal, Karner-Hanusch, Judith, Heinimann, Karl, Marra, Giancarlo, Jiricny, Josef and Bartosova, Zdena (2008) Background: In the workup of patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC), detection of loss of heterozygosity (LOH) could help pinpoint the mismatch-repair (MMR) gene carrying the germline mutation, but analysis of microsatellite markers has... Interplay of DNA repair pathways controls methylation damage toxicity in Saccharomyces cerevisiae Cejka, Petr and Jiricny, Josef (2008) Methylating agents of S(N)1 type are widely used in cancer chemotherapy, but their mode of action is poorly understood. In particular, it is unclear how the primary cytotoxic lesion, O(6)-methylguanine ((Me)G), causes cell death. One hypothesis stipulates that binding of mismatch... The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis Menigatti, Mirco, Cattaneo, Elisa, Sabates-Bellver, Jacob, Ilinsky, Valery V., Went, Philip, Buffoli, Federico, Marquez, Victor E., Jiricny, Josef and Marra, Giancarlo (2009) Background Tumor development in the human colon is commonly accompanied by epigenetic changes, such as DNA methylation and chromatin modifications. These alterations result in significant, inheritable changes in gene expression that contribute to the selection of tumor... The Uracil DNA Glycosylase UdgB of Mycobacterium smegmatis Protects the Organism from the Mutagenic Effects of Cytosine and Adenine Deamination Wanner, Roger M., Castor, Dennis, Güthlein, Carolin, Böttger, Erik C., Springer, Burkhard and Jiricny, Josef (2009) Spontaneous hydrolytic deamination of DNA bases represents a considerable mutagenic threat to all organisms, particularly those living in extreme habitats. Cytosine is readily deaminated to uracil, which base pairs with adenine during replication, and most organisms encode at least...