Academic Journal
Beta human papillomavirus 8E6 promotes alternative end joining
| العنوان: | Beta human papillomavirus 8E6 promotes alternative end joining |
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| المؤلفون: | Changkun Hu, Taylor Bugbee, Rachel Palinski, Ibukun A Akinyemi, Michael T McIntosh, Thomas MacCarthy, Sumita Bhaduri-McIntosh, Nicholas Wallace |
| المصدر: | eLife, Vol 12 (2023) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | beta-HPV, DSB repair, MMEJ, P300, NHEJ, HR, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Double strand breaks (DSBs) are one of the most lethal DNA lesions in cells. The E6 protein of beta-human papillomavirus (HPV8 E6) impairs two critical DSB repair pathways: homologous recombination (HR) and non-homologous end joining (NHEJ). However, HPV8 E6 only delays DSB repair. How DSBs are repaired in cells with HPV8 E6 remains to be studied. We hypothesize that HPV8 E6 promotes a less commonly used DSB repair pathway, alternative end joining (Alt-EJ). Using CAS9-based Alt-EJ reporters, we show that HPV8 E6 promotes Alt-EJ. Further, using small molecule inhibitors, CRISPR/CAS9 gene knockout, and HPV8 E6 mutant, we find that HPV8 E6 promotes Alt-EJ by binding p300, an acetyltransferase that facilitates DSB repair by HR and NHEJ. At least some of this repair occurs through a subset of Alt-EJ known as polymerase theta dependent end joining. Finally, whole genome sequencing analysis showed HPV8 E6 caused an increased frequency of deletions bearing the microhomology signatures of Alt-EJ. This study fills the knowledge gap of how DSB is repaired in cells with HPV8 E6 and the mutagenic consequences of HPV8 E6 mediated p300 destabilization. Broadly, this study supports the hypothesis that beta-HPV promotes cancer formation by increasing genomic instability. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/81923; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.81923 |
| URL الوصول: | https://doaj.org/article/b54c18b5addc4591aac934765ee5ce95 |
| رقم الانضمام: | edsdoj.b54c18b5addc4591aac934765ee5ce95 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.81923 |