Structure of the Rad50 DNA double‐strand break repair protein in complex with DNA

Autor: Florian Seifert, Carolin Direnberger, Heidi Feldmann, Katja Lammens, Karl-Peter Hopfner, Anna Rojowska
Rok vydání: 2014
Předmět:
Models
Molecular
HMG-box
Protein Conformation
Base pair
Molecular Sequence Data
Saccharomyces cerevisiae
Biology
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Bacterial Proteins
Thermotoga maritima
Protein–DNA interaction
Amino Acid Sequence
Molecular Biology
Replication protein A
030304 developmental biology
Genetics
chemistry.chemical_classification
0303 health sciences
DNA ligase
Binding Sites
Crystallography
DNA clamp
Base Sequence
General Immunology and Microbiology
General Neuroscience
Telomere Homeostasis
Articles
DNA
Sequence Analysis
DNA
DNA-binding domain
Protein Structure
Tertiary
Cell biology
DNA-Binding Proteins
enzymes and coenzymes (carbohydrates)
DNA Repair Enzymes
chemistry
Multiprotein Complexes
DNA supercoil
biological phenomena
cell phenomena
and immunity
Sequence Alignment
030217 neurology & neurosurgery
Zdroj: The EMBO Journal
ISSN: 1460-2075
0261-4189
Popis: The Mre11-Rad50 nuclease-ATPase is an evolutionarily conserved multifunctional DNA double-strand break (DSB) repair factor. Mre11-Rad50's mechanism in the processing, tethering, and signaling of DSBs is unclear, in part because we lack a structural framework for its interaction with DNA in different functional states. We determined the crystal structure of Thermotoga maritima Rad50(NBD) (nucleotide-binding domain) in complex with Mre11(HLH) (helix-loop-helix domain), AMPPNP, and double-stranded DNA. DNA binds between both coiled-coil domains of the Rad50 dimer with main interactions to a strand-loop-helix motif on the NBD. Our analysis suggests that this motif on Rad50 does not directly recognize DNA ends and binds internal sites on DNA. Functional studies reveal that DNA binding to Rad50 is not critical for DNA double-strand break repair but is important for telomere maintenance. In summary, we provide a structural framework for DNA binding to Rad50 in the ATP-bound state.
Databáze: OpenAIRE
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