In this section
@article{Serrao:2015:10.1186/s12977-015-0167-3,
author = {Serrao, E and Ballandras-Colas, A and Cherepanov, P and Maertens, GN and Engelman, AN},
doi = {10.1186/s12977-015-0167-3},
journal = {Retrovirology},
title = {Key determinants of target DNA recognition by retroviral intasomes},
url = {http://dx.doi.org/10.1186/s12977-015-0167-3},
volume = {12},
year = {2015}
}
TY - JOUR
AB - Background: Retroviral integration favors weakly conserved palindrome sequences at the sites of viral DNA joiningand generates a short (4–6 bp) duplication of host DNA flanking the provirus. We previously determined two keyparameters that underlie the target DNA preference for prototype foamy virus (PFV) and human immunodeficiencyvirus type 1 (HIV-1) integration: flexible pyrimidine (Y)/purine (R) dinucleotide steps at the centers of the integrationsites, and base contacts with specific integrase residues, such as Ala188 in PFV integrase and Ser119 in HIV-1 integrase.Here we examined the dinucleotide preference profiles of a range of retroviruses and correlated these findings withrespect to length of target site duplication (TSD).Results: Integration datasets covering six viral genera and the three lengths of TSD were accessed from the literatureor generated in this work. All viruses exhibited significant enrichments of flexible YR and/or selection against rigid RYdinucleotide steps at the centers of integration sites, and the magnitude of this enrichment inversely correlated withTSD length. The DNA sequence environments of in vivo-generated HIV-1 and PFV sites were consistent with integrationinto nucleosomes, however, the local sequence preferences were largely independent of target DNA chromatinization.Integration sites derived from cells infected with the gammaretrovirus reticuloendotheliosis virus strain A (Rev-A),which yields a 5 bp TSD, revealed the targeting of global chromatin features most similar to those of Moloneymurine leukemia virus, which yields a 4 bp duplication. In vitro assays revealed that Rev-A integrase interacts withand is catalytically stimulated by cellular bromodomain containing 4 protein.Conclusions: Retroviral integrases have likely evolved to bend target DNA to fit scissile phosphodiester bondsinto two active sites for integration, and viruses that cut target DNA with a 6 bp stagger may not need to bendDNA as sharply as viruses tha
AU - Serrao,E
AU - Ballandras-Colas,A
AU - Cherepanov,P
AU - Maertens,GN
AU - Engelman,AN
DO - 10.1186/s12977-015-0167-3
PY - 2015///
SN - 1742-4690
TI - Key determinants of target DNA recognition by retroviral intasomes
T2 - Retrovirology
UR - http://dx.doi.org/10.1186/s12977-015-0167-3
UR - http://hdl.handle.net/10044/1/27803
VL - 12
ER -
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