TY - JOUR
T1 - Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM complex
AU - Wang, Feng
AU - Yang, Yuting
AU - Singh, Thiyam Ramsing
AU - Busygina, Valeria
AU - Guo, Rong
AU - Wan, Ke
AU - Wang, Weidong
AU - Sung, Patrick
AU - Meetei, Amom Ruhikanta
AU - Lei, Ming
N1 - Funding Information:
We thank Y. Chen and J. Sun for help at various stages of the project. M.L. is a Howard Hughes Medical Institute Early Career Scientist. This work was supported by NIH grants (GM 083015-01 to M.L., HL084082 to A.R.M., and ES015632 and ES07061 to P.S.), an American Cancer Society Research Scholar Award (to M.L.), and the Intramural Research Program of the National Institute on Aging (AG000688-07 to W.W.). The General Medicine and Cancer Institutes Collaborative Access Team has been funded in whole or in part with federal funds from the National Cancer Institute (grant Y1-CO-1020) and the National Institute of General Medical Science (grant Y1-GM-1104). Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract no. DE-AC02-06CH11357.
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.str.2010.06.008
DO - 10.1016/j.str.2010.06.008
M3 - Article
C2 - 20826342
AN - SCOPUS:77956336552
SN - 0969-2126
VL - 18
SP - 1159
EP - 1170
JO - Structure
JF - Structure
IS - 9
ER -