Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM complex.
Mutations in BLM, a RecQ-like helicase, are linked to the autosomal recessive cancer-prone disorder Bloom's syndrome. BLM associates with topoisomerase (Topo) IIIα, RMI1, and RMI2 to form the BLM complex that is essential for genome stability. The RMI1-RMI2 heterodimer stimulates the dissolution of double Holliday junction into non-crossover recombinants mediated by BLM-Topo IIIα and is essential for stabilizing the BLM complex. However, the molecular basis of these functions of RMI1 and RMI2 remains unclear. Here we report the crystal structures of multiple domains of RMI1-RMI2, providing direct confirmation of the existence of three oligonucleotide/oligosaccharide binding (OB)-folds in RMI1-RMI2. Our structural and biochemical analyses revealed an unexpected insertion motif in RMI1N-OB, which is important for stimulating the dHJ dissolution. We also revealed the structural basis of the interaction between RMI1C-OB and RMI2-OB and demonstrated the functional importance of the RMI1-RMI2 interaction in genome stability maintenance.
Wang
Feng
F
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yang
Yuting
Y
Singh
Thiyam Ramsing
TR
Busygina
Valeria
V
Guo
Rong
R
Wan
Ke
K
Wang
Weidong
W
Sung
Patrick
P
Meetei
Amom Ruhikanta
AR
Lei
Ming
M
D001816:Bloom Syndrome / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004264:DNA Topoisomerases, Type I / Q000737:chemistry; D045566:DNA, Cruciform / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D021122:Protein Subunits
D002352:Carrier Proteins; D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; C501527:RMI1 protein, human; C533196:RMI2 protein, human; D004264:DNA Topoisomerases, Type I
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