The Integrase of the Long Terminal Repeat-Retrotransposon Tf1 Has a Chromodomain That Modulates Integrase Activities

Department of Cell and Developmental Biology, Tel Aviv University, Tell Afif, Tel Aviv, Israel
Journal of Biological Chemistry (Impact Factor: 4.57). 12/2005; 280(47):39086-94. DOI: 10.1074/jbc.M506363200
Source: PubMed


Chromodomains in a variety of proteins mediate the formation of heterochromatin by interacting directly with histone H3, DNA, or RNA. A diverse family of long terminal repeat (LTR)-retrotransposons possesses chromodomains in their integrases (IN), suggesting that the chromodomains may control integration. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is highly active and possesses a chromodomain in the COOH terminus of its IN. To test this chromodomain for a role in integration, recombinant INs with and without the chromodomain were assayed for activity in in vitro reactions. The full-length IN had integration activity with oligonucleotide substrates that modeled both the insertion reaction and a reverse reaction known as disintegration. The INs of retroviruses possess an additional activity termed 3' processing that must remove 2-3 nucleotides from the 3' ends of the viral cDNA before insertion can occur. These additional nucleotides are added during reverse transcription because of the position of the minus strand primer downstream of the LTR. The position of the primer for Tf1 suggests no nucleotides are added 3' of the LTR. It was therefore surprising that Tf1 IN was capable of 3' cleavage. The most unexpected result reported here was that the IN lacking the chromodomain had significantly higher activity and substantially reduced substrate specificity. These results reveal that both the activity and specificity of enzymes can be modulated by their chromodomains.

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    • "The transposition activity of the MAGGY retrotransposon of the rice blast fungus Magnaporthe oryzae dramatically decreased with the loss or alteration of the chromodomain [19]. On the other hand, the chromointegrase of the Tf1 LTR retrotransposon from Schizosaccharomyces pombe that lacks the chromodomain demonstrated a significantly higher activity and a substantially reduced substrate specificity [20]. As was demonstrated recently, the MAGGY chromodomain interacts with H3K9me2 and H3K9me3 in a similar way compared to the HP1 " classical " chromodomain. "
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    • "However, it remains to be determined whether endogenous small RNAs (such as piRNAs that silence retrotransposons) elicit transcriptional gene silencing in mammals. It is important to note that several retrotransposons are targeted to integrate within regions of heterochromatin by a chromodomain motif within the integrase protein (Kordis 2005; Hizi et al. 2005; Gao et al. 2008). It has recently been demonstrated in flies that Piwi, which binds piRNAs to mediate transposon silencing, interacts directly with the chromodomain protein HP1a (Brower-Toland et al. 2007), and that this interaction is required for transcriptional gene silencing. "
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