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By Frank J. Dixon

Study Institute of Scripps sanatorium, l. a. Jolla. learn within the box. For investigators. 19 participants, 6 U.S.

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Mol. Genet. 2,1589-1595. , and Srivastava, P. K. (1993). Tumor rejection antigen gp96/grp94 is an ATPase: Implications for protein folding and antigen presentation. EMBO J. 12, 3143-3151. , Yewdell, J. , and Bennink, J. R. (1994). Trimming of antigenic peptides in an early secretory compartment. J. Exp. Med. 180, 2389-2394. Lowe, J.. , and Huber, R. (1:95). Crystal structure of the 20s proteasome from the Archaeon T. 4 A resolution. Science 268, 533-539. , Koster, A. , and Baumeister, W. (1993).

These proteins fall into the importin-a, family of factors required for transport of proteins into the nucleus (Gorlich and Mattaj, 1996), and it is not yet clear whether they have any role other than nuclear transport in relation to the RAG system. B. , 1996; Jackson and Jeggo, 1995; Weaver, 1995). This linkage first became apparent from the properties of the mouse scid mutation. , 1986), later work showed that its effects were not restricted to lymphoid cells. Also, V( D)J recombination in scid fibroblasts transfected with RAG expression 48 MARTIN GELLERT vectors displays the same defects as those found in scid lymphoid cells.

Concomitantly, many broken signal ends appear at Igrc (as much as 40% of the DNA is ) and Gellert, 1995). Coding joints accumulate at broken at J K ~(Ramsden about the same rate as signal ends; here again, the joining of signal and coding ends is uncoupled, and coding ends are joined much faster. The signal ends are quite stable at high temperature (for more than a day) but are efficientlyjoined when the cells are returned to low temperature. Thus, the signal ends are proper intermediates in recombination (Ramsden and Gellert, 1995).

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