Genetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells

ABSTRACT DNA lesions in the template strand block synthesis by replicative DNA polymerases (Pols). Eukaryotic cells possess a number of specialized translesion synthesis (TLS) Pols with the ability to replicate through DNA lesions. The Epstein-Barr virus (EBV), a member of the herpesvirus family, in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jung-Hoon Yoon, Satya Prakash, Louise Prakash
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/466e71c4c55c4061bc77cbd147b19476
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:466e71c4c55c4061bc77cbd147b19476
record_format	dspace
spelling	oai:doaj.org-article:466e71c4c55c4061bc77cbd147b194762021-11-15T15:39:12ZGenetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells10.1128/mBio.00271-122150-7511https://doaj.org/article/466e71c4c55c4061bc77cbd147b194762012-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00271-12https://doaj.org/toc/2150-7511ABSTRACT DNA lesions in the template strand block synthesis by replicative DNA polymerases (Pols). Eukaryotic cells possess a number of specialized translesion synthesis (TLS) Pols with the ability to replicate through DNA lesions. The Epstein-Barr virus (EBV), a member of the herpesvirus family, infects human B cells and is maintained there as an extrachromosomal replicon, replicating once per cycle during S phase. Except for the requirement of the virus-encoded origin-binding protein EBNA1, replication of plasmids containing the EBV origin of replication (oriP) is controlled by the same cellular processes that govern chromosomal replication. Since replication of EBV plasmid closely mimics that of human chromosomal DNA, in this study we examined the genetic control of TLS in a duplex plasmid in which bidirectional replication initiates from an EBV oriP origin and a UV-induced cis-syn TT dimer is placed on the leading- or the lagging-strand DNA template. Here we show that TLS occurs equally frequently on both the DNA strands of EBV plasmid and that the requirements of TLS Pols are the same regardless of which DNA strand carries the lesion. We discuss the implications of these observations for TLS mechanisms that operate on the two DNA strands during chromosomal replication and conclude that the same genetic mechanisms govern TLS during the replication of the leading and the lagging DNA strands in human cells. IMPORTANCE Since replication of EBV (Epstein-Barr virus) origin-based plasmids appropriates the cellular machinery for all the steps of replication, our observations that the same genetic mechanisms govern translesion synthesis (TLS) on the two DNA strands of EBV plasmids imply that the requirements of TLS Pols are not affected by any of the differences in the replicative Pols or in other proteins that may be used for the replication of the two DNA strands in human cells. These findings also have important implications for evaluating the significance of results of TLS studies with the SV40 origin-based plasmids that we have reported previously, in which we showed that TLS occurs similarly on the two DNA strands. Since the genetic control of TLS in SV40 plasmids resembles that in EBV plasmids, we conclude that TLS studies with the SV40 plasmids are as informative of TLS mechanisms that operate during cellular replication as those with the EBV plasmids.Jung-Hoon YoonSatya PrakashLouise PrakashAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 5 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jung-Hoon Yoon Satya Prakash Louise Prakash Genetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells
description	ABSTRACT DNA lesions in the template strand block synthesis by replicative DNA polymerases (Pols). Eukaryotic cells possess a number of specialized translesion synthesis (TLS) Pols with the ability to replicate through DNA lesions. The Epstein-Barr virus (EBV), a member of the herpesvirus family, infects human B cells and is maintained there as an extrachromosomal replicon, replicating once per cycle during S phase. Except for the requirement of the virus-encoded origin-binding protein EBNA1, replication of plasmids containing the EBV origin of replication (oriP) is controlled by the same cellular processes that govern chromosomal replication. Since replication of EBV plasmid closely mimics that of human chromosomal DNA, in this study we examined the genetic control of TLS in a duplex plasmid in which bidirectional replication initiates from an EBV oriP origin and a UV-induced cis-syn TT dimer is placed on the leading- or the lagging-strand DNA template. Here we show that TLS occurs equally frequently on both the DNA strands of EBV plasmid and that the requirements of TLS Pols are the same regardless of which DNA strand carries the lesion. We discuss the implications of these observations for TLS mechanisms that operate on the two DNA strands during chromosomal replication and conclude that the same genetic mechanisms govern TLS during the replication of the leading and the lagging DNA strands in human cells. IMPORTANCE Since replication of EBV (Epstein-Barr virus) origin-based plasmids appropriates the cellular machinery for all the steps of replication, our observations that the same genetic mechanisms govern translesion synthesis (TLS) on the two DNA strands of EBV plasmids imply that the requirements of TLS Pols are not affected by any of the differences in the replicative Pols or in other proteins that may be used for the replication of the two DNA strands in human cells. These findings also have important implications for evaluating the significance of results of TLS studies with the SV40 origin-based plasmids that we have reported previously, in which we showed that TLS occurs similarly on the two DNA strands. Since the genetic control of TLS in SV40 plasmids resembles that in EBV plasmids, we conclude that TLS studies with the SV40 plasmids are as informative of TLS mechanisms that operate during cellular replication as those with the EBV plasmids.
format	article
author	Jung-Hoon Yoon Satya Prakash Louise Prakash
author_facet	Jung-Hoon Yoon Satya Prakash Louise Prakash
author_sort	Jung-Hoon Yoon
title	Genetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells
title_short	Genetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells
title_full	Genetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells
title_fullStr	Genetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells
title_full_unstemmed	Genetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells
title_sort	genetic control of translesion synthesis on leading and lagging dna strands in plasmids derived from epstein-barr virus in human cells
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/466e71c4c55c4061bc77cbd147b19476
work_keys_str_mv	AT junghoonyoon geneticcontroloftranslesionsynthesisonleadingandlaggingdnastrandsinplasmidsderivedfromepsteinbarrvirusinhumancells AT satyaprakash geneticcontroloftranslesionsynthesisonleadingandlaggingdnastrandsinplasmidsderivedfromepsteinbarrvirusinhumancells AT louiseprakash geneticcontroloftranslesionsynthesisonleadingandlaggingdnastrandsinplasmidsderivedfromepsteinbarrvirusinhumancells
_version_	1718427761987551232

Genetic Control of Translesion Synthesis on Leading and Lagging DNA Strands in Plasmids Derived from Epstein-Barr Virus in Human Cells

Ejemplares similares