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Pohang, South Korea

Wei J.-D.,Korea University | Kim J.-Y.,Korea University | Kim A.-K.,Panbionet Corporation | Jang S.K.,Pohang University of Science and Technology | Kim J.-H.,Korea University
Journal of Biological Chemistry

Background: The regulatory mechanism of BLT2 is largely unknown. Results: RanBPM interacts with BLT2 and inhibits BLT2-induced ROS generation and chemotaxis. Conclusion: Our findings suggest that RanBPM acts as a negative regulator of BLT2. Significance: Identification of regulators would provide better understanding of BLT2 signaling and potentially various BLT2- associated inflammatory pathogenesis. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Source

Choe J.,Korea University | Kim K.M.,Korea University | Park S.,Korea University | Lee Y.K.,Panbionet Corporation | And 5 more authors.
Nucleic Acids Research

The translation of mammalian messenger RNAs (mRNAs) can be driven by either cap-binding proteins 80 and 20 (CBP80/20) or eukaryotic translation initiation factor (eIF)4E. Although CBP80/20-dependent translation (CT) is known to be coupled to an mRNA surveillance mechanism termed nonsense-mediated mRNA decay (NMD), its molecular mechanism and biological role remain obscure. Here, using a yeast two-hybrid screening system, we identify a stem-loop binding protein (SLBP) that binds to a stem-loop structure at the 3′-end of the replication-dependent histone mRNA as a CT initiation factor (CTIF)-interacting protein. SLBP preferentially associates with the CT complex of histone mRNAs, but not with the eIF4E-depedent translation (ET) complex. Several lines of evidence indicate that rapid degradation of histone mRNA on the inhibition of DNA replication largely takes place during CT and not ET, which has been previously unappreciated. Furthermore, the ratio of CBP80/20-bound histone mRNA to eIF4E-bound histone mRNA is larger than the ratio of CBP80/20-bound polyadenylated β-actin or eEF2 mRNA to eIF4E-bound polyadenylated β-actin or eEF2 mRNA, respectively. The collective findings suggest that mRNAs harboring a different 3′-end use a different mechanism of translation initiation, expanding the repertoire of CT as a step for determining the fate of histone mRNAs. © 2012 The Author(s). Source

Sung S.,Pohang University of Science and Technology | Li F.,University of Texas Health Science Center at San Antonio | Park Y.B.,Pohang University of Science and Technology | Kim J.S.,Pohang University of Science and Technology | And 6 more authors.
EMBO Journal

The Mre11-Rad50-Nbs1 (MRN) complex plays important roles in sensing DNA damage, as well as in resecting and tethering DNA ends, and thus participates in double-strand break repair. An earlier structure of Mre11 bound to a short duplex DNA molecule suggested that each Mre11 in a dimer recognizes one DNA duplex to bridge two DNA ends at a short distance. Here, we provide an alternative DNA recognition model based on the structures of Methanococcus jannaschii Mre11 (MjMre11) bound to longer DNA molecules, which may more accurately reflect a broken chromosome. An extended stretch of B-form DNA asymmetrically runs across the whole dimer, with each end of this DNA molecule being recognized by an individual Mre11 monomer. DNA binding induces rigid-body rotation of the Mre11 dimer, which could facilitate melting of the DNA end and its juxtaposition to an active site of Mre11. The identified Mre11 interface binding DNA duplex ends is structurally conserved and shown to functionally contribute to efficient resection, non-homologous end joining, and tolerance to DNA-damaging agents when other resection enzymes are absent. Together, the structural, biochemical, and genetic findings presented here offer new insights into how Mre11 recognizes damaged DNA and facilitates DNA repair. Synopsis DNA end tethering and nucleolytic resection at double-strand break sites are key functions of the conserved MRN (Mre11-Rad50-Nbs1) complex mediated by its Mre11 subunit. New crystal structures of Mre11-DNA complexes reveal an alternative model for Mre11-DNA complexes, in which Mre11 dimers recognize a single stretch of longer, more physiological DNA substrate. Structures of Mre11 bound to longer DNA molecules show that the Mre11 dimer as a whole recognizes one single molecule of extended B-form DNA. A structurally conserved basic region constituting the DNA binding interface is important for binding and cleavage of substrates, as well as for in vivo repair functions. Mre11 quaternary structural changes may facilitate DNA end melting and guide broken ends to the nuclease active site. DNA end tethering may require further oligomerization of Mre11 dimers. Crystal structures reveal the importance of a novel, conserved interface through which the dimeric MRN complex subunit Mre11 binds a single molecule of longer DNA representing its physiological substrate. © 2014 The Authors. Source

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