Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling
Human papillomaviruses (HPV) require the activation of the DNA damage response (DDR) in order to undergo a successful life cycle. This activation presents a challenge for the virus and the infected cell: how does viral and host replication proceed in the presence of a DDR that ordinarily arrests rep...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/9/10/268 |
| _version_ | 1818248771528556544 |
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| author | Molly L. Bristol Dipon Das Iain M. Morgan |
| author_facet | Molly L. Bristol Dipon Das Iain M. Morgan |
| author_sort | Molly L. Bristol |
| collection | DOAJ |
| description | Human papillomaviruses (HPV) require the activation of the DNA damage response (DDR) in order to undergo a successful life cycle. This activation presents a challenge for the virus and the infected cell: how does viral and host replication proceed in the presence of a DDR that ordinarily arrests replication; and how do HPV16 infected cells retain the ability to proliferate in the presence of a DDR that ordinarily arrests the cell cycle? This raises a further question: why do HPV activate the DDR? The answers to these questions are only partially understood; a full understanding could identify novel therapeutic strategies to target HPV cancers. Here, we propose that the rapid replication of an 8 kb double stranded circular genome during infection creates aberrant DNA structures that attract and activate DDR proteins. Therefore, HPV replication in the presence of an active DDR is a necessity for a successful viral life cycle in order to resolve these DNA structures on viral genomes; without an active DDR, successful replication of the viral genome would not proceed. We discuss the essential role of TopBP1 in this process and also how viral and cellular replication proceeds in HPV infected cells in the presence of DDR signals. |
| first_indexed | 2024-12-12T15:25:54Z |
| format | Article |
| id | doaj.art-96349e0b0f214689b2ccb30c609e3332 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-12T15:25:54Z |
| publishDate | 2017-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-96349e0b0f214689b2ccb30c609e33322022-12-22T00:20:16ZengMDPI AGViruses1999-49152017-09-0191026810.3390/v9100268v9100268Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR SignalingMolly L. Bristol0Dipon Das1Iain M. Morgan2VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USAVCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USAVCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USAHuman papillomaviruses (HPV) require the activation of the DNA damage response (DDR) in order to undergo a successful life cycle. This activation presents a challenge for the virus and the infected cell: how does viral and host replication proceed in the presence of a DDR that ordinarily arrests replication; and how do HPV16 infected cells retain the ability to proliferate in the presence of a DDR that ordinarily arrests the cell cycle? This raises a further question: why do HPV activate the DDR? The answers to these questions are only partially understood; a full understanding could identify novel therapeutic strategies to target HPV cancers. Here, we propose that the rapid replication of an 8 kb double stranded circular genome during infection creates aberrant DNA structures that attract and activate DDR proteins. Therefore, HPV replication in the presence of an active DDR is a necessity for a successful viral life cycle in order to resolve these DNA structures on viral genomes; without an active DDR, successful replication of the viral genome would not proceed. We discuss the essential role of TopBP1 in this process and also how viral and cellular replication proceeds in HPV infected cells in the presence of DDR signals.https://www.mdpi.com/1999-4915/9/10/268HPVhuman papillomavirusreplicationinitiationlife cycleDNA damage responseTopBP1E1E2ATM (ataxia-telangiectasia mutated)ATR (ataxia telangiectasia and Rad3 related)DNA damage signalingcervical cancerhead and neck cancerhomologous recombinationMRN (Mre11-Rad50-Nbs1) |
| spellingShingle | Molly L. Bristol Dipon Das Iain M. Morgan Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling Viruses HPV human papillomavirus replication initiation life cycle DNA damage response TopBP1 E1 E2 ATM (ataxia-telangiectasia mutated) ATR (ataxia telangiectasia and Rad3 related) DNA damage signaling cervical cancer head and neck cancer homologous recombination MRN (Mre11-Rad50-Nbs1) |
| title | Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling |
| title_full | Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling |
| title_fullStr | Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling |
| title_full_unstemmed | Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling |
| title_short | Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling |
| title_sort | why human papillomaviruses activate the dna damage response ddr and how cellular and viral replication persists in the presence of ddr signaling |
| topic | HPV human papillomavirus replication initiation life cycle DNA damage response TopBP1 E1 E2 ATM (ataxia-telangiectasia mutated) ATR (ataxia telangiectasia and Rad3 related) DNA damage signaling cervical cancer head and neck cancer homologous recombination MRN (Mre11-Rad50-Nbs1) |
| url | https://www.mdpi.com/1999-4915/9/10/268 |
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