dc.creator | Cui, Xiuji | es |
dc.creator | McAllister, Rebecca | es |
dc.creator | Boregowda, Rajeev | es |
dc.creator | Sohn, Ji A. | es |
dc.creator | Cortés Ledesma, Felipe | es |
dc.creator | Caldecott, Keith W. | es |
dc.creator | Seeger, Christoph | es |
dc.creator | Hu, Jianming | es |
dc.date.accessioned | 2019-01-31T10:53:12Z | |
dc.date.available | 2019-01-31T10:53:12Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Cui, X., McAllister, R., Boregowda, R., Sohn, J.A., Cortés Ledesma, F., Caldecott, K.W.,...,Hu, J. (2015). Does tyrosyl DNA phosphodiesterase-2 play a role in hepatitis B virus genome repair?. PLoS ONE, 10, 1-15. | |
dc.identifier.issn | 1932-6203 (electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/82292 | |
dc.description.abstract | Hepatitis B virus (HBV) replication and persistence are sustained by a nuclear episome, the
covalently closed circular (CCC) DNA, which serves as the transcriptional template for all
viral RNAs. CCC DNA is converted from a relaxed circular (RC) DNA in the virion early during
infection as well as from RC DNA in intracellular progeny nucleocapsids via an intracellular
amplification pathway. Current antiviral therapies suppress viral replication but cannot
eliminate CCC DNA. Thus, persistence of CCC DNA remains an obstacle toward curing
chronic HBV infection. Unfortunately, very little is known about how CCC DNA is formed.
CCC DNA formation requires removal of the virally encoded reverse transcriptase (RT) protein
from the 5’ end of the minus strand of RC DNA. Tyrosyl DNA phosphodiesterase-2
(Tdp2) was recently identified as the enzyme responsible for cleavage of tyrosyl-5’ DNA
linkages formed between topoisomerase II and cellular DNA. Because the RT-DNA linkage
is also a 5’ DNA-phosphotyrosyl bond, it has been hypothesized that Tdp2 might be one of
several elusive host factors required for CCC DNA formation. Therefore, we examined the
role of Tdp2 in RC DNA deproteination and CCC DNA formation. We demonstrated Tdp2
can cleave the tyrosyl-minus strand DNA linkage using authentic HBV RC DNA isolated
from nucleocapsids and using RT covalently linked to short minus strand DNA produced in
vitro. On the other hand, our results showed that Tdp2 gene knockout did not block CCC
DNA formation during HBV infection of permissive human hepatoma cells and did not prevent
intracellular amplification of duck hepatitis B virus CCC DNA. These results indicate
that although Tdp2 can remove the RT covalently linked to the 5’ end of the HBV minus
strand DNA in vitro, this protein might not be required for CCC DNA formation in vivo. | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.relation.ispartof | PLoS ONE, 10, 1-15. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | Does tyrosyl DNA phosphodiesterase-2 play a role in hepatitis B virus genome repair? | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.publisherversion | http://dx.doi.org/10.1371/journal.pone.0128401 | es |
dc.identifier.doi | 10.1371/journal.pone.0128401 | es |
idus.format.extent | 15 p. | es |
dc.journaltitle | PLoS ONE | es |
dc.publication.volumen | 10 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 15 | es |