Rad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge

Hisashi Tatebe; Chew Theng Lim; Hiroki Konno; Kazuhiro Shiozaki; Akira Shinohara; Takayuki Uchihashi; Asako Furukohri

doi:10.1038/s41467-019-14025-0

Rad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge

Nat Commun. 2020 Jan 17;11(1):370. doi: 10.1038/s41467-019-14025-0.

Authors

Hisashi Tatebe¹, Chew Theng Lim¹, Hiroki Konno², Kazuhiro Shiozaki^{1

3}, Akira Shinohara⁴, Takayuki Uchihashi^{5

6}, Asako Furukohri⁷

Affiliations

¹ Nara Institute of Science and Technology, Graduate School of Biological Sciences, Ikoma, Nara, 630-0192, Japan.
² WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
³ Department of Microbiology and Molecular Genetics, University of California, Davis, CA, 95616, USA.
⁴ Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan.
⁵ Department of Physics, Nagoya University, Nagoya, 464-8602, Japan. [email protected].
⁶ Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, 444-8787, Japan. [email protected].
⁷ Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan. [email protected].

Abstract

The human Mre11/Rad50 complex is one of the key factors in genome maintenance pathways. Previous nanoscale imaging by atomic force microscopy (AFM) showed that the ring-like structure of the human Mre11/Rad50 complex transiently opens at the zinc hook of Rad50. However, imaging of the human Mre11/Rad50 complex by high-speed AFM shows that the Rad50 coiled-coil arms are consistently bridged by the dimerized hooks while the Mre11/Rad50 ring opens by disconnecting the head domains; resembling other SMC proteins such as cohesin or condensin. These architectural features are conserved in the yeast and bacterial Mre11/Rad50 complexes. Yeast strains harboring the chimeric Mre11/Rad50 complex containing the SMC hinge of bacterial condensin MukB instead of the RAD50 hook properly functions in DNA repair. We propose that the basic role of the Rad50 hook is similar to that of the SMC hinge, which serves as rather stable dimerization interface.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acid Anhydride Hydrolases / chemistry*
Acid Anhydride Hydrolases / metabolism
Adenosine Triphosphatases
Animals
Cell Cycle Proteins / chemistry*
Cell Cycle Proteins / metabolism
Chromosomal Proteins, Non-Histone / chemistry*
Chromosomal Proteins, Non-Histone / metabolism
Cohesins
DNA Breaks, Double-Stranded
DNA Repair
DNA-Binding Proteins / chemistry*
DNA-Binding Proteins / metabolism
Dimerization*
Escherichia coli / metabolism
Homologous Recombination
Humans
MRE11 Homologue Protein / chemistry
MRE11 Homologue Protein / metabolism
Microscopy, Atomic Force
Multiprotein Complexes
Nuclear Proteins / chemistry
Nuclear Proteins / metabolism
Protein Binding
Protein Conformation
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins / metabolism
Sf9 Cells
Zinc / metabolism*

Substances

Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
MRE11 protein, human
Multiprotein Complexes
NBN protein, human
Nuclear Proteins
Saccharomyces cerevisiae Proteins
condensin complexes
MRE11 Homologue Protein
Acid Anhydride Hydrolases
RAD50 protein, human
Adenosine Triphosphatases
Zinc