Cell-cycle-dependent EBNA1-DNA crosslinking promotes replication termination at oriP and viral episome maintenance
Copyright © 2020 Elsevier Inc. All rights reserved..
Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that persists as a multicopy episome in proliferating host cells. Episome maintenance is strictly dependent on EBNA1, a sequence-specific DNA-binding protein with no known enzymatic activities. Here, we show that EBNA1 forms a cell cycle-dependent DNA crosslink with the EBV origin of plasmid replication oriP. EBNA1 tyrosine 518 (Y518) is essential for crosslinking to oriP and functionally required for episome maintenance and generation of EBV-transformed lymphoblastoid cell lines (LCLs). Mechanistically, Y518 is required for replication fork termination at oriP in vivo and for formation of SDS-resistant complexes in vitro. EBNA1-DNA crosslinking corresponds to single-strand endonuclease activity specific to DNA structures enriched at replication-termination sites, such as 4-way junctions. These findings reveal that EBNA1 forms tyrosine-dependent DNA-protein crosslinks and single-strand cleavage at oriP required for replication termination and viral episome maintenance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:184 |
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| Enthalten in: |
Cell - 184(2021), 3 vom: 04. Feb., Seite 643-654.e13 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dheekollu, Jayaraju [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.08.2021 Date Revised 05.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2020.12.022 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM320443124 |
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| 100 | 1 | |a Dheekollu, Jayaraju |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cell-cycle-dependent EBNA1-DNA crosslinking promotes replication termination at oriP and viral episome maintenance |
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| 500 | |a Date Completed 24.08.2021 | ||
| 500 | |a Date Revised 05.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that persists as a multicopy episome in proliferating host cells. Episome maintenance is strictly dependent on EBNA1, a sequence-specific DNA-binding protein with no known enzymatic activities. Here, we show that EBNA1 forms a cell cycle-dependent DNA crosslink with the EBV origin of plasmid replication oriP. EBNA1 tyrosine 518 (Y518) is essential for crosslinking to oriP and functionally required for episome maintenance and generation of EBV-transformed lymphoblastoid cell lines (LCLs). Mechanistically, Y518 is required for replication fork termination at oriP in vivo and for formation of SDS-resistant complexes in vitro. EBNA1-DNA crosslinking corresponds to single-strand endonuclease activity specific to DNA structures enriched at replication-termination sites, such as 4-way junctions. These findings reveal that EBNA1 forms tyrosine-dependent DNA-protein crosslinks and single-strand cleavage at oriP required for replication termination and viral episome maintenance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a DNA-binding domain | |
| 650 | 4 | |a DNA-protein adducts | |
| 650 | 4 | |a EBNA1 | |
| 650 | 4 | |a Epstein-Barr virus | |
| 650 | 4 | |a RADAR | |
| 650 | 4 | |a episome | |
| 650 | 4 | |a herpesvirus | |
| 650 | 4 | |a oriP | |
| 650 | 4 | |a plasmid maintenance | |
| 650 | 4 | |a tyrosine resolvase | |
| 650 | 4 | |a viral latency | |
| 650 | 7 | |a Cross-Linking Reagents |2 NLM | |
| 650 | 7 | |a DNA Adducts |2 NLM | |
| 650 | 7 | |a DNA, Viral |2 NLM | |
| 650 | 7 | |a Epstein-Barr Virus Nuclear Antigens |2 NLM | |
| 650 | 7 | |a Tyrosine |2 NLM | |
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| 650 | 7 | |a Endonucleases |2 NLM | |
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| 650 | 7 | |a EBV-encoded nuclear antigen 1 |2 NLM | |
| 650 | 7 | |a O5GA75RST7 |2 NLM | |
| 700 | 1 | |a Wiedmer, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Ayyanathan, Kasirajan |e verfasserin |4 aut | |
| 700 | 1 | |a Deakyne, Julianna S |e verfasserin |4 aut | |
| 700 | 1 | |a Messick, Troy E |e verfasserin |4 aut | |
| 700 | 1 | |a Lieberman, Paul M |e verfasserin |4 aut | |
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