The endonuclease Ankle1 requires its LEM and GIY-YIG motifs for DNA cleavage in vivo
| Autor: | Roland Foisner, Juliane Braun, Siegfried Knasmüller, Medini Manohar Ghodgaonkar, Josef Jiricny, Veronika Ehrlich, Dennis Castor, Andreas Brachner, Livija Zlopasa, Josef Gotzmann |
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| Přispěvatelé: | University of Zurich, Foisner, Roland |
| Rok vydání: | 2012 |
| Předmět: |
Cytoplasm
Hematopoietic System Amino Acid Motifs Emerin Polymerase Chain Reaction Article Conserved sequence Cell Line 1307 Cell Biology 03 medical and health sciences Endonuclease 0302 clinical medicine Animals Humans Immunoprecipitation Nuclear protein DNA Cleavage Conserved Sequence 030304 developmental biology Cell Nucleus 0303 health sciences Nucleoplasm biology Gene Expression Profiling 10061 Institute of Molecular Cancer Research Cell Biology Endonucleases Molecular biology Chromatin Transport protein Cell biology Protein Structure Tertiary Protein Transport Organ Specificity 030220 oncology & carcinogenesis biology.protein 570 Life sciences Ankyrin repeat DNA Damage Signal Transduction |
| Zdroj: | Journal of cell science |
| ISSN: | 1477-9137 |
| Popis: | The LEM domain (for lamina-associated polypeptide, emerin, MAN1 domain) defines a group of nuclear proteins that bind chromatin through interaction of the LEM motif with the conserved DNA crosslinking protein, barrier-to-autointegration factor (BAF). Here, we describe a LEM protein annotated in databases as ‘Ankyrin repeat and LEM domain-containing protein 1’ (Ankle1). We show that Ankle1 is conserved in metazoans and contains a unique C-terminal GIY-YIG motif that confers endonuclease activity in vitro and in vivo. In mammals, Ankle1 is predominantly expressed in hematopoietic tissues. Although most characterized LEM proteins are components of the inner nuclear membrane, ectopic Ankle1 shuttles between cytoplasm and nucleus. Ankle1 enriched in the nucleoplasm induces DNA cleavage and DNA damage response. This activity requires both the catalytic C-terminal GIY-YIG domain and the LEM motif, which binds chromatin via BAF. Hence, Ankle1 is an unusual LEM protein with a GIY-YIG-type endonuclease activity in higher eukaryotes. |
| Databáze: | OpenAIRE |
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