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closeReferee Comments: Referee 2
Posted by PLOS_ONE_Group on 13 Jul 2007 at 18:27 GMT
Reviewer 2's Review
“This manuscript extend previous findings from the same group (ref. 21) by showing that HIV integrase (in addition to PFV IN) has an endonuclease activity allowing the cleavage of the LTR-LTR junction of 2-LTR circles. The cleavage of this imperfect palindromic sequence displays a relative sequence specificity. Efficient cleavage requires oligomerization of IN to form a tetramer (figure 4), while dimers of IN are sufficient for the 3' processing activity. More precisely, dimers of IN display some endonuclease activity, but do not share the specificity of tetramers for the LTR-LTR junction (figure 6).
IN cleavage of this junction would elevate 2-LTR circles from dead end products to the rank of processing intermediate of integration. The authors acknowledge, however, that the product of internal cleavage differs (in terms of size of the staggered ends) from the one demonstrated to be competent for integration. The manuscript is relevant to the field and data shown here can be analyzed and interpreted in the context of an abundant literature. Data are clearly presented.”
N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.