Toth Group

Prof. Dr. Attila Tóth

Attila Tóth is a mouse geneticist and cell biologist, focusing on the molecular mechanisms that safeguard genome stability and enable correct reduction of chromosome numbers in the mammalian germline during meiosis. He has discovered multiple novel meiotic mouse proteins, and generated corresponding mutant mouse models to investigate the mechanism of meiotic recombination and its quality control. Most relevant to the current project, he identified HORMAD2 as a key component of meiotic checkpoints, and he characterized the role of HORMAD2 in monitoring non-synapsed chromosomes and ATR signaling resulting in oocyte death. His work has provided evidence for distinct checkpoints that monitor chromosomal synapsis and DNA repair in oocytes. He provides several mouse models, and extensive know-how in mouse genetics.

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Publications

  • 1. Chromosomal synapsis defects can trigger oocyte apoptosis without elevating numbers of persistent DNA breaks above wild-type levels. Ravindranathan R, Raveendran K, Papanikos F, San-Segundo PA, Tóth A. Nucleic Acids Res. 2022 May 17:gkac355. doi: 10.1093/nar/gkac355. Online ahead of print. PMID: 35580048

  • 2. Four-pronged negative feedback of DSB machinery in meiotic DNA-break control in mice. Dereli I, Stanzione M, Olmeda F, Papanikos F, Baumann M, Demir S, Carofiglio F, Lange J, de Massy B, Baarends WM, Turner J, Rulands S, Tóth A. Nucleic Acids Res. 2021 Mar 18;49(5):2609-2628. doi: 10.1093/nar/gkab082. PMID: 33619545

  • 3. Proline-rich protein PRR19 functions with cyclin-like CNTD1 to promote meiotic crossing over in mouse. Bondarieva A, Raveendran K, Telychko V, Rao HBDP, Ravindranathan R, Zorzompokou C, Finsterbusch F, Dereli I, Papanikos F, Tränkner D, Schleiffer A, Fei JF, Klimova A, Ito M, Kulkarni DS, Roeder I, Hunter N, Tóth A. Nat Commun. 2020 Jun 18;11(1):3101. doi: 10.1038/s41467-020- 16885-3. PMID: 32555348

  • 4. Mouse ANKRD31 Regulates Spatiotemporal Patterning of Meiotic Recombination Initiation and Ensures Recombination between X and Y Sex Chromosomes. Papanikos F, Clément JAJ, Testa E, Ravindranathan R, Grey C, Dereli I, Bondarieva A, Valerio- Cabrera S, Stanzione M, Schleiffer A, Jansa P, Lustyk D, Fei JF, Adams IR, Forejt J, Barchi M, de Massy B, Toth A. Mol Cell. 2019 Jun 6;74(5):1069-1085.e11. doi: 10.1016/j.molcel.2019.03.022. Epub 2019 Apr 15. PMID: 31000436

  • 5. ATR is a multifunctional regulator of male mouse meiosis. Widger A, Mahadevaiah SK, Lange J, ElInati E, Zohren J, Hirota T, Pacheco S, Maldonado-Linares A, Stanzione M, Ojarikre O, Maciulyte V, de Rooij DG, Tóth A, Roig I, Keeney S, Turner JMA. Nat Commun. 2018 Jul 5;9(1):2621. doi: 10.1038/s41467-018-04850-0.

  • 6. Repair of exogenous DNA double-strand breaks promotes chromosome synapsis in SPO11- mutant mouse meiocytes, and is altered in the absence of HORMAD1. Carofiglio F, Sleddens- Linkels E, Wassenaar E, Inagaki A, van Cappellen WA, Grootegoed JA, Tóth A, Baarends WM. DNA Repair (Amst). 2018 Mar;63:25-38. doi: 10.1016/j.dnarep.2018.01.007. Epub 2018 Jan 31.

  • 7. The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding. Ye Q, Kim DH, Dereli I, Rosenberg SC, Hagemann G, Herzog F, Tóth A, Cleveland DW, Corbett KD. EMBO J. 2017 Jun 28. pii: e201797291. doi: 10.15252/embj.201797291. [Epub ahead of print]

  • 8. Alignment of homologous chromosomes and effective repair of programmed DNA double-strand breaks during mouse meiosis require the minichromosome maintenance domain containing 2 (MCMDC2) protein. Finsterbusch F, Ravindranathan R, Dereli I, Stanzione M, Tränkner D, Tóth A PLoS Genet. 2016 Oct 19;12(10):e1006393. doi: 10.1371/journal.pgen.1006393.

  • 9. Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice. Stanzione M, Baumann M, Papanikos F, Dereli I, Lange J, Ramlal A, Tränkner D, Shibuya H, de Massy B, Watanabe Y, Jasin M, Keeney S, Tóth A Nature Cell Biology 2016 Oct

  • 10. Mammalian meiotic silencing exhibits sexually dimorphic features. Cloutier JM, Mahadevaiah SK, ElInati E, Tóth A, Turner J. Chromosoma. 2016 Jun;125(2):215-26. doi: 10.1007/s00412-015- 0568-z. Epub 2015 Dec 28. 11. The enigmatic meiotic dense body and its newly discovered component, SCML1, are dispensable for fertility and gametogenesis in mice. Papanikos F*, Daniel K*, Goercharn-Ramlal A*, Fei JF, Kurth T, Wojtasz L, Dereli I, Fu J, Penninger J, Habermann B, Surani A, Stewart AF, Tóth A Chromosoma. 2016 May 10. [Epub ahead of print] *These authors contributed equally to this work.

  • 11. Histone H2AFX Links Meiotic Chromosome Asynapsis to Prophase I Oocyte Loss in Mammals. Cloutier JM, Mahadevaiah SK, ElInati E, Nussenzweig A, Tóth A, Turner JM. PLoS Genet. 2015 Oct 28;11(10):e1005462. doi: 10.1371/journal.pgen.1005462. eCollection 2015 Oct.

  • 12. Mouse CCDC79 (TERB1) is a meiosis-specific telomere associated protein. Daniel K, Tränkner D, Wojtasz L, Shibuya H, Watanabe Y, Alsheimer M, Tóth A. BMC Cell Biol. 2014 May 22;15:17. doi: 10.1186/1471-2121-15-17.

  • 13. ATR acts stage specifically to regulate multiple aspects of mammalian meiotic silencing. Royo H, Prosser H, Ruzankina Y, Mahadevaiah SK, Cloutier JM, Baumann M, Fukuda T, Höög C, Tóth A, de Rooij DG, Bradley A, Brown EJ, Turner JM. Genes & Development 2013 Jul 1;27(13):1484-94.

  • 14. Meiotic DNA double-strand breaks and chromosome asynapsis in mice are monitored by distinct HORMAD2-independent and -dependent mechanisms. Wojtasz L, Cloutier JM, Baumann M, Daniel K, Varga J, Fu J, Anastassiadis K, Stewart AF, Reményi A, Turner JM, Tóth A. Genes & Development 2012 May 1;26(9):958-73.

  • 15. Meiotic homologous chromosome alignment and its surveillance are controlled by mouse HORMAD1. Daniel K, Lange J, Hached K, Fu J, Anastassiadis K, Roig I, Cooke HJ, Stewart AF, Wassmann K, Jasin J, Keeney S, Tóth A. Nature Cell Biology 2011 May;13(5):599-610. Epub 2011 Apr 10

  • 16. Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. Wojtasz L*, Daniel K*, Roig I, Bolcun-Filas E, Xu H, Boonsanay V, Eckmann CR, Cooke HJ, Jasin M, Keeney S, McKay MJ, Tóth A. PLoS Genet. 2009 Oct;5(10):e1000702. Epub 2009 Oct 23. *These authors contributed equally to this work. 

  • 17. Fluorescence activated cell sorting of live female germ cells and somatic cells of the mouse fetal gonad based on forward and side scattering. Wojtasz L, Daniel K, Tóth A. Cytometry A. 2009 Jun;75(6):547-53.

  • 18. Functional genomics identifies monopolin: a kinetochore protein required for segregation of homologs during meiosis I. Tóth A*, Rabitsch KP*, Gálová M, Schleiffer A, Buonomo SB, Nasmyth K. Cell. 2000 Dec 22;103(7):1155-68. *These authors contributed equally to this work.

  • 19. Yeast cohesin complex requires a conserved protein, Eco1p(Ctf7), to establish cohesion between sister chromatids during DNA replication. Tóth A, Ciosk R, Uhlmann F, Galova M, Schleiffer A, Nasmyth K. Genes & Development 1999 Feb 1;13(3):320-33.