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The life cycle of sexually reproducing eukaryotes depends on two specialized chromosome segregation programs: mitosis and meiosis. Whereas mitosis drives cellular proliferation and the stable propagation of the genome, meiosis promotes genetic diversity and the formation of haploid gametes, which combine at fertilization to restore the diploid state. Remarkably, both genome stability and genetic diversity depend on the cell’s ability to repair damaged chromosomes using homologous recombination.
We study how cells rewire their DNA repair machinery in order to: 1) promote genetic diversity and haploidisation during meiosis; 2) prevent genomic instability - and cancer - during mitotic proliferation; 3) ensure the efficient disengagement of recombination intermediates prior chromosome segregation and cell division.
Our group uses a combination of approaches (cell biology, biochemistry and structural biology) and model systems (budding yeast, mouse and human tissue culture) to investigate how cells rewire DNA repair according to the specialized needs of mitotic proliferation and meiosis.
Joao Matos was born and raised in Portugal. He moved to Germany in 2003, to start his PhD work with Wolfgang Zachariae (MPI-CBG). In 2009, he moved to England, to carry out postdoctoral work with Stephen West (London Research Institute). In 2014, Joao was appointed Assistant Professor at the ETH, Switzerland. He joined the University of Vienna in 2020, as Professor of Cell and Developmental Biology.
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Organisms often have to ensure their survival during periods of unfavorable environmental conditions. Through the process of meiosis, budding yeast cells haploidize their genome and package it into environmentally resistant spores. In their publication in Cell, Joao Matos and his team discovered that metabolic enzymes essential for the recovery from spore dormancy form protein filaments during meiosis. In collaboration with the Pilhofer lab at the Eidgenössische Technische Hochschule (ETH) in Zurich, Matos and his team developed a novel workflow that combines the preparation of cell spreads with multimodal imaging that enabled the study of these filaments with unprecedented detail. The work implicates a previously unanticipated organization of proteins in the cell that permits long periods of dormancy. Read more
Sexual reproduction involves the formation of gametes, specialized male and female reproductive cells. Gamete formation involves a process called meiosis where DNA is segregated into daughter cells, each containing half the genomic content of the adult cells. In their study published in Developmental Cell, Joao Matos and his collaborators characterized the composition and phosphorylation status of the proteome during meiosis, using budding yeast as a model system. They found that sequential waves of protein expression and phosphorylation rewire the proteome to enable gametogenesis. They also discovered that mitochondrial enzymes, such as ATP synthase and Aldehyde dehydrogenase, are regulated by phosphorylation during gametogenesis. Read more
The Bloom (BLM) DNA helicase is an important enzyme in DNA repair and the maintenance of genome stability. Mutations in BLM are associated with Bloom’s Syndrome, a disease characterized by growth defects and increased susceptibility to cancer. In recent work published in Science Advances, we have elucidated how cells regulate the correct timing of BLM activity during the mitotic cell division program.
When the MUS81 DNA endonuclease is left uncontrolled in human cells, it breaks up chromosomes into tiny pieces. This is damaging to cells, but useful for killing tumours. We are trying to understand the underlying mechanism. (image credit: Jiradet Gloggnitzer)
Holliday Junctions are important DNA repair intermediates that form during meiosis. The junction is represented by a swiss bread specialty made from yeast dough. It is just about to be cut by the Yen1/GEN1 resolvase (hands and knife) to allow faithful segregation of the two chromosomes. The timing of the cut needs to be tightly regulated (wrist watch). (image credit: Meret Arter)
We have used affinity proteomics to characterize the composition and interaction landscape of 7 DNA repair enzymes during mitotic proliferation and meiosis. We reported a concerted and context-specific rewiring of the interactomes and reveal meiosis-specific network components with roles in crossing-over.
Anthropomorphic artistic illustration of the ‘powerful’ RecQ helicase Sgs1 (in blue) displacing the two DNA strands within a DNA molecule. (image credit: C. Matos).
Robert Bodo
PhD Student +43 1 4277 56231
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Felix Hartmann
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Adrian Henggeler
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Nataliia Kashko
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Uladzislava Khauratovich
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Joao Matos
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Lucija Orlic
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Nathan Palmer
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Rajvi Patel
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Anzhela Pavlova
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Vasiliki Petroulaki
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Daniel Velikov
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Rahel Wettstein
Senior PostDoc +43 1 4277 56231
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Martin Xaver
PostDoc +43 1 4277 56231
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https://www.maxperutzlabs.ac.at/news/latest-news/l/all-eyes-on-the-proteome-100380
https://www.maxperutzlabs.ac.at/news/latest-news/l/survival-of-the-filamentous-100379
https://www.maxperutzlabs.ac.at/news/latest-news/l/new-funding-for-meiosis-research-100248
https://www.maxperutzlabs.ac.at/news/latest-news/l/getting-out-of-your-comfort-zone-1-100227
We are looking for talented, ambitious scientists at various levels. Postdoc, PhD and Master student positions are currently available. Please contact Joao and include a summary of previous research interests, a statement with your motivation to join our team, and the names of potential referees in your application.
Waves of regulated protein expression and phosphorylation rewire the proteome to drive gametogenesis in budding yeast.
Wettstein Rahel, Hugener Jannik, Gillet Ludovic, Hernández-Armenta Yi, Henggeler Adrian, Xu Jingwei, van Gerwen Julian, Wollweber Florian, Arter Meret, Aebersold Ruedi, Beltrao Pedro, Pilhofer Martin, Matos Joao
FilamentID reveals the composition and function of metabolic enzyme polymers during gametogenesis.
Hugener Jannik, Xu Jingwei, Wettstein Rahel, Ioannidi Lydia, Velikov Daniel, Wollweber Florian, Henggeler Adrian, Matos Joao, Pilhofer Martin
Meiotic nuclear pore complex remodeling provides key insights into nuclear basket organization.
King Grant A, Wettstein Rahel, Varberg Joseph M, Chetlapalli Keerthana, Walsh Madison E, Gillet Ludovic C J, Hernández-Armenta Claudia, Beltrao Pedro, Aebersold Ruedi, Jaspersen Sue L, Matos Joao, Ünal Elçin
The CDK1-TOPBP1-PLK1 axis regulates the Bloom's syndrome helicase BLM to suppress crossover recombination in somatic cells.
Balbo Pogliano Chiara, Ceppi Ilaria, Giovannini Sara, Petroulaki Vasiliki, Palmer Nathan, Uliana Federico, Gatti Marco, Kasaciunaite Kristina, Freire Raimundo, Seidel Ralf, Altmeyer Matthias, Cejka Petr, Matos Joao
Regulation of the MLH1-MLH3 endonuclease in meiosis.
Cannavo Elda, Sanchez Aurore, Anand Roopesh, Ranjha Lepakshi, Hugener Jannik, Adam Céline, Acharya Ananya, Weyland Nicolas, Aran-Guiu Xavier, Charbonnier Jean-Baptiste, Hoffmann Eva R, Borde Valérie, Matos Joao, Cejka Petr
Phosphorylation of the RecQ Helicase Sgs1/BLM Controls Its DNA Unwinding Activity during Meiosis and Mitosis.
Grigaitis Rokas, Ranjha Lepakshi, Wild Philipp, Kasaciunaite Kristina, Ceppi Ilaria, Kissling Vera, Henggeler Adrian, Susperregui Aitor, Peter Matthias, Seidel Ralf, Cejka Petr, Matos Joao
Network Rewiring of Homologous Recombination Enzymes during Mitotic Proliferation and Meiosis.
Wild Philipp, Susperregui Aitor, Piazza Ilaria, Dörig Christian, Oke Ashwini, Arter Meret, Yamaguchi Miyuki, Hilditch Alexander T, Vuina Karla, Chan Ki Choi, Gromova Tatiana, Haber James E, Fung Jennifer C, Picotti Paola, Matos Joao
Regulated Crossing-Over Requires Inactivation of Yen1/GEN1 Resolvase during Meiotic Prophase I.
Arter Meret, Hurtado-Nieves Vanesa, Oke Ashwini, Zhuge Tangna, Wettstein Rahel, Fung Jennifer C, Blanco Miguel G, Matos Joao
A Mechanism for Controlled Breakage of Under-replicated Chromosomes during Mitosis.
Duda Heike, Arter Meret, Gloggnitzer Jiradet, Teloni Federico, Wild Philipp, Blanco Miguel G, Altmeyer Matthias, Matos Joao
Dual control of Yen1 nuclease activity and cellular localization by Cdk and Cdc14 prevents genome instability.
Blanco Miguel G, Matos Joao, West Stephen C
Cell-cycle kinases coordinate the resolution of recombination intermediates with chromosome segregation.
Matos Joao, Blanco Miguel G, West Stephen C
Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis.
Matos Joao, Blanco Miguel G, Maslen Sarah, Skehel J Mark, West Stephen C
Dbf4-dependent CDC7 kinase links DNA replication to the segregation of homologous chromosomes in meiosis I.
Matos Joao, Lipp Jesse J, Bogdanova Aliona, Guillot Sylvine, Okaz Elwy, Junqueira Magno, Shevchenko Andrej, Zachariae Wolfgang
Monopolar attachment of sister kinetochores at meiosis I requires casein kinase 1.
Petronczki Mark, Matos Joao, Mori Saori, Gregan Juraj, Bogdanova Aliona, Schwickart Martin, Mechtler Karl, Shirahige Katsuhiko, Zachariae Wolfgang, Nasmyth Kim
