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Institute of Molecular Genetics of the Czech Academy of Sciences
Institute of Molecular Genetics of the Czech Academy of Sciences

Selected Results

Key features of vertebrate head development have their origins in a common ancestor

Amphioxus studies demonstrated that key features of vertebrate head development originated in the common ancestor of all chordates.

The study demonstrated that essential structures for vertebrate head development evolved in the common ancestor of all chordates. Research on amphioxus identified cells resembling the neural crest and prechordal plate, which play a role in the head formation. The findings enhance our understanding of chordate evolution and vertebrate head developmental mechanisms.

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This image illustrates the evolutionary relationships among different groups of animals, including echinoderms, lancelets, tunicates, and vertebrates.
The image illustrates the evolutionary relationships among echinoderms, lancelets, tunicates, and vertebrates. It shows that the key developmental programs for the prechordal plate and the neural crest, which are essential for the formation of the head, have their roots in the ancestors of chordates, which include all vertebrates, humans included.
PublicationMarkos A, Kubovciak J, Mikula Mrstakova S, Zitova A, Paces J, Machacova S, Kozmik-Jr Z, Kozmik Z, Kozmikova I: Cell type and regulatory analysis in amphioxus illuminates evolutionary origin of the vertebrate head. Nat Commun 2024 15(1): 8859. [pubmed] [doi]
ContactIryna Kozmiková, (+420) 774 798 198, iryna.kozmikova@img.cas.cz

Structural basis of MICAL autoinhibition

The study reveals the structure of the human MICAL1 protein, resolved using cryo-electron microscopy, and describes the molecular mechanism of its inhibition, which is crucial for maintaining the structural integrity of the cell.

MICAL proteins play a key role in the breakdown of actin filaments, enabling cells to change shape and move. Precise control of their activity is crucial, as uncontrolled action could compromise the structural integrity of the cell. This study reveals the structure of the human MICAL1 protein, resolved using cryo-electron microscopy. The structure demonstrates how MICAL1 remains “locked” in an inactive state until it is activated by a signal to cleave actin filaments.

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a) Cryo-electron microscopy map of the MICAL1 protein showing its shape and key domains. b) Detailed view of the MICAL1 protein structure in its autoinhibited state.
a) Cryo-electron microscopy map of the MICAL1 protein showing its shape and key domains.
b) Detailed view of the MICAL1 protein structure in its autoinhibited state.
PublicationHorvath M, Schrofel A, Kowalska K, Sabo J, Vlasak J, Nourisanami F, Sobol M, Pinkas D, Knapp K, Koupilova N, Novacek J, Veverka V, Lansky Z, Rozbesky D: Structural basis of MICAL autoinhibition. Nat Commun 2024 15(1): 9810. [pubmed] [doi]
ContactDaniel Rozbeský, (+420) 325 873 104, daniel.rozbesky@img.cas.cz
Cooperating subjectsFaculty of Science, Charles University, Prague, Czech Republic
CEITEC (Central European Institute of Technology), Brno, Czech Republic
Institute of Biotechnology of the Czech Academy of Sciences, Prague, Czech Republic

RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin

In this study, we have described a novel molecular pathway in human cells, in which protein RAD18 controls DNA repair by homologous recombination and prevents genome instability.

DNA breaks must be precisely repaired by homologous recombination to prevent genome instability. This process can only take place at a stage of the cell cycle when the genomic DNA has already been replicated. The newly described complex of RAD18 and SLF1/2 proteins recognizes chromatin around the replicated DNA and allows recruitment of the SMC5/6 complex to the DNA breaks, which is essential for completion of homologous recombination. Disruption of these processes can lead to cancer.

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a) Super-resolution microscopy images of human cells exposed to ionizing radiation. b) Model of a signalling pathway in which the RAD18-SLF1/2 protein complex recognizes nucleosomes with already replicated genomic DNA and allows bringing the SMC5/6 complex into the vicinity of a DNA double-strand break.
a) Super-resolution microscopy images of human cells exposed to ionizing radiation. The cell nucleus is indicated in dashed lines, and the square cut-outs indicate the sites of individual DNA breaks. Green and purple mark the localization of the indicated proteins near the DNA damage. BRCA1 and RAD18 proteins are in the immediate vicinity of the breaks, 53BP1 is present at the edge of the lesions.
b) Model of a signalling pathway in which the RAD18-SLF1/2 protein complex recognizes nucleosomes with already replicated genomic DNA and allows bringing the SMC5/6 complex into the vicinity of a DNA double-strand break.
PublicationPalek M, Palkova N, CZECANCA consortium, Kleiblova P, Kleibl Z, Macurek L: RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin. Nucleic Acids Res 2024. [pubmed] [doi]
ContactLibor Macůrek, (+420) 296 443 210, libor.macurek@img.cas.cz
Cooperating subjectFirst Faculty of Medicine, Charles University, Prague, Czech Republic
General University Hospital in Prague, Czech Republic