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Volume 272, Number 17, Issue of April 25, 1997 pp. 11402-11407
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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The Translin Ring Specifically Recognizes DNA Ends at Recombination Hot Spots in the Human Genome

(Received for publication, February 21, 1996, and in revised form, December 20, 1996)

Masataka Kasai , Takao Matsuzaki ^¶ , Katsuo Katayanagi ^¶ , Akira Omori , Richard T. Maziarz ^** , Jack L. Strominger , Katsunori Aoki ^§§ and Kenji Suzuki ^¶¶

From the Departments of  Immunology and ^¶¶ Pathology, National Institute of Health, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162, Japan, ^¶ Mitsubishi Chemical Corporation, 1000 Kamoshida, Aobaku, Yokohama 227, Japan,  Mitsubishi-Kasei Institute of Life Sciences, Minami-ooya 11, Machida-shi, Tokyo 194, Japan, ^** Division of Hematology and Oncology, Oregon Health Sciences University and the Portland Veterans Affairs Medical Center, Portland, Oregon 97207,  Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, and ^§§ The First Department of Internal Medicine, School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan

We previously showed that consensus sequences exist at the chromosomal breakpoints in lymphoid malignancies and that these sequences are specifically recognized by a novel DNA binding protein, Translin. In the present study, the native form of Translin was established to be a ring-shaped structure by electron microscopy and crystallographic studies. It was also determined that this multimeric Translin formed by the subunits is responsible for its binding to target sequences situated only at single-stranded DNA ends. Furthermore, DNA-damaging reagents were found to initiate a signaling pathway for the active nuclear transport of Translin. The results support the hypothesis that staggered breaks occur at recombination hot spots and Translin has a pivotal function in recognition of the generated single-stranded DNA ends.

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