A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation
Human papillomaviruses (HPV) are causative agents in around 5% of all human cancers. To identify and develop new targeted HPV therapeutics we must enhance our understanding of the viral life cycle and how it interacts with the host. The HPV E2 protein dimerizes and binds to 12bp target sequences in...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Tumour Virus Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666679024000156 |
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| author | Apurva T. Prabhakar Iain M. Morgan |
| author_facet | Apurva T. Prabhakar Iain M. Morgan |
| author_sort | Apurva T. Prabhakar |
| collection | DOAJ |
| description | Human papillomaviruses (HPV) are causative agents in around 5% of all human cancers. To identify and develop new targeted HPV therapeutics we must enhance our understanding of the viral life cycle and how it interacts with the host. The HPV E2 protein dimerizes and binds to 12bp target sequences in the viral genome and segregates the viral genome during mitosis. In this function, E2 binds to the viral genome and the host chromatin simultaneously, ensuring viral genomes reside in daughter nuclei following cell division. We have demonstrated that a mitotic interaction between E2 and the DNA damage response (DDR) protein TOPBP1 is required for E2 segregation function. In non-infected cells, following DNA damage, TOPBP1 is recruited to the mitotic host genome via interaction with MDC1 and this interaction protects DNA integrity during mitosis. Recently we demonstrated that the E2-TOPBP1 interaction activates the DNA damage response (DDR) during mitosis independently from external stimuli, promoting TOPBP1 interaction with mitotic chromatin and therefore segregation of the viral genome. Therefore, the virus has hijacked an existing host mechanism in order to segregate the viral genome. This intricate E2 function will be described and discussed. |
| format | Article |
| id | doaj-art-c83f2df36f5b4e5e8f50f4ce816df31c |
| institution | OA Journals |
| issn | 2666-6790 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Tumour Virus Research |
| spelling | doaj-art-c83f2df36f5b4e5e8f50f4ce816df31c2025-08-20T02:38:05ZengElsevierTumour Virus Research2666-67902024-12-011820029110.1016/j.tvr.2024.200291A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregationApurva T. Prabhakar0Iain M. Morgan1Virginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, VA, 23298, USAVirginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, VA, 23298, USA; VCU Massey Cancer Center, Richmond, VA, 23298, USA; Corresponding author. Virginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, VA, 23298, USA.Human papillomaviruses (HPV) are causative agents in around 5% of all human cancers. To identify and develop new targeted HPV therapeutics we must enhance our understanding of the viral life cycle and how it interacts with the host. The HPV E2 protein dimerizes and binds to 12bp target sequences in the viral genome and segregates the viral genome during mitosis. In this function, E2 binds to the viral genome and the host chromatin simultaneously, ensuring viral genomes reside in daughter nuclei following cell division. We have demonstrated that a mitotic interaction between E2 and the DNA damage response (DDR) protein TOPBP1 is required for E2 segregation function. In non-infected cells, following DNA damage, TOPBP1 is recruited to the mitotic host genome via interaction with MDC1 and this interaction protects DNA integrity during mitosis. Recently we demonstrated that the E2-TOPBP1 interaction activates the DNA damage response (DDR) during mitosis independently from external stimuli, promoting TOPBP1 interaction with mitotic chromatin and therefore segregation of the viral genome. Therefore, the virus has hijacked an existing host mechanism in order to segregate the viral genome. This intricate E2 function will be described and discussed.http://www.sciencedirect.com/science/article/pii/S2666679024000156 |
| spellingShingle | Apurva T. Prabhakar Iain M. Morgan A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation Tumour Virus Research |
| title | A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation |
| title_full | A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation |
| title_fullStr | A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation |
| title_full_unstemmed | A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation |
| title_short | A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation |
| title_sort | new role for human papillomavirus 16 e2 mitotic activation of the dna damage response to promote viral genome segregation |
| url | http://www.sciencedirect.com/science/article/pii/S2666679024000156 |
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