title: The endonuclease Ankle1 requires its LEM and GIY-YIG motifs for DNA cleavage in vivo.
abstract: 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.
authors.affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Dr. Bohr-Gasse 9, A-1030, Vienna,  Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brachner
authors.forename: Juliane
authors.initials: J
authors.lastname: Braun
authors.forename: Medini
authors.initials: M
authors.lastname: Ghodgaonkar
authors.forename: Dennis
authors.initials: D
authors.lastname: Castor
authors.forename: Livija
authors.initials: L
authors.lastname: Zlopasa
authors.forename: Veronika
authors.initials: V
authors.lastname: Ehrlich
authors.forename: Josef
authors.initials: J
authors.lastname: Jiricny
authors.forename: Josef
authors.initials: J
authors.lastname: Gotzmann
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmüller
authors.forename: Roland
authors.initials: R
authors.lastname: Foisner
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism; D053837:DNA Cleavage; D004249:DNA Damage; D004720:Endonucleases / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006413:Hematopoietic System / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: C579363:ANKLE1 protein, human; D004720:Endonucleases