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Regulation of Epstein-Barr virus OriP replication by poly(ADP-ribose) polymerase 1.
J Virol. 2010 May; 84(10):4988-97.JV

Abstract

Poly(ADP-ribose) polymerase (PARP) is an abundant, chromatin-associated, NAD-dependent enzyme that functions in multiple chromosomal processes, including DNA replication and chromatin remodeling. The Epstein-Barr virus (EBV) origin of plasmid replication (OriP) is a dynamic genetic element that confers stable episome maintenance, DNA replication initiation, and chromatin organization functions. OriP function depends on the EBV-encoded origin binding protein EBNA1. We have previously shown that EBNA1 is subject to negative regulation by poly(ADP-ribosyl)ation (PARylation). We now show that PARP1 physically associates with OriP in latently EBV-infected B cells. Short hairpin RNA depletion of PARP1 enhances OriP replication activity and increases EBNA1, origin recognition complex 2 (ORC2), and minichromosome maintenance complex (MCM) association with OriP. Pharmacological inhibitors of PARP1 enhance OriP plasmid maintenance and increase EBNA1, ORC2, and MCM3 occupancy at OriP. PARylation in vitro inhibits ORC2 recruitment and remodels telomere repeat factor (TRF) binding at the dyad symmetry (DS) element of OriP. Purified PARP1 can ribosylate EBNA1 at multiple sites throughout its amino terminus but not in the carboxy-terminal DNA binding domain. We also show that EBNA1 linking regions (LR1 and LR2) can bind directly to oligomers of PAR. We propose that PARP1-dependent PARylation of EBNA1 and adjacently bound TRF2 induces structural changes at the DS element that reduce EBNA1 DNA binding affinity and functional recruitment of ORC.

Authors+Show Affiliations

The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20219917

Citation

Tempera, Italo, et al. "Regulation of Epstein-Barr Virus OriP Replication By poly(ADP-ribose) Polymerase 1." Journal of Virology, vol. 84, no. 10, 2010, pp. 4988-97.
Tempera I, Deng Z, Atanasiu C, et al. Regulation of Epstein-Barr virus OriP replication by poly(ADP-ribose) polymerase 1. J Virol. 2010;84(10):4988-97.
Tempera, I., Deng, Z., Atanasiu, C., Chen, C. J., D'Erme, M., & Lieberman, P. M. (2010). Regulation of Epstein-Barr virus OriP replication by poly(ADP-ribose) polymerase 1. Journal of Virology, 84(10), 4988-97. https://doi.org/10.1128/JVI.02333-09
Tempera I, et al. Regulation of Epstein-Barr Virus OriP Replication By poly(ADP-ribose) Polymerase 1. J Virol. 2010;84(10):4988-97. PubMed PMID: 20219917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of Epstein-Barr virus OriP replication by poly(ADP-ribose) polymerase 1. AU - Tempera,Italo, AU - Deng,Zhong, AU - Atanasiu,Constandache, AU - Chen,Chi-Ju, AU - D'Erme,Maria, AU - Lieberman,Paul M, Y1 - 2010/03/10/ PY - 2010/3/12/entrez PY - 2010/3/12/pubmed PY - 2010/5/5/medline SP - 4988 EP - 97 JF - Journal of virology JO - J Virol VL - 84 IS - 10 N2 - Poly(ADP-ribose) polymerase (PARP) is an abundant, chromatin-associated, NAD-dependent enzyme that functions in multiple chromosomal processes, including DNA replication and chromatin remodeling. The Epstein-Barr virus (EBV) origin of plasmid replication (OriP) is a dynamic genetic element that confers stable episome maintenance, DNA replication initiation, and chromatin organization functions. OriP function depends on the EBV-encoded origin binding protein EBNA1. We have previously shown that EBNA1 is subject to negative regulation by poly(ADP-ribosyl)ation (PARylation). We now show that PARP1 physically associates with OriP in latently EBV-infected B cells. Short hairpin RNA depletion of PARP1 enhances OriP replication activity and increases EBNA1, origin recognition complex 2 (ORC2), and minichromosome maintenance complex (MCM) association with OriP. Pharmacological inhibitors of PARP1 enhance OriP plasmid maintenance and increase EBNA1, ORC2, and MCM3 occupancy at OriP. PARylation in vitro inhibits ORC2 recruitment and remodels telomere repeat factor (TRF) binding at the dyad symmetry (DS) element of OriP. Purified PARP1 can ribosylate EBNA1 at multiple sites throughout its amino terminus but not in the carboxy-terminal DNA binding domain. We also show that EBNA1 linking regions (LR1 and LR2) can bind directly to oligomers of PAR. We propose that PARP1-dependent PARylation of EBNA1 and adjacently bound TRF2 induces structural changes at the DS element that reduce EBNA1 DNA binding affinity and functional recruitment of ORC. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/20219917/Regulation_of_Epstein_Barr_virus_OriP_replication_by_poly_ADP_ribose__polymerase_1_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=20219917 DB - PRIME DP - Unbound Medicine ER -