Noncatalytic, N-terminal Domains of DNA Polymerase Lambda Affect Its Cellular Localization and DNA Damage Response
| العنوان: | Noncatalytic, N-terminal Domains of DNA Polymerase Lambda Affect Its Cellular Localization and DNA Damage Response |
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| المؤلفون: | David J. Taggart, Anthony A. Stephenson, Zucai Suo |
| المصدر: | Chemical Research in Toxicology. 30:1240-1249 |
| بيانات النشر: | American Chemical Society (ACS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, DNA polymerase, DNA damage, Toxicology, Article, Catalysis, Cell Line, Mice, 03 medical and health sciences, Animals, Humans, NLS, Cloning, Molecular, DNA Polymerase beta, Cellular localization, Cell Nucleus, Cloning, biology, General Medicine, DNA polymerase lambda, Chromatin, 030104 developmental biology, Biochemistry, biology.protein, Nuclear localization sequence, DNA Damage |
| الوصف: | Specialized DNA polymerases, such as DNA polymerase lambda (Polλ), are important players in DNA damage tolerance and repair pathways. Knowing how DNA polymerases are regulated and recruited to sites of DNA damage is imperative to understanding these pathways. Recent work has suggested that Polλ plays a role in several distinct DNA damage tolerance and repair pathways. In this paper, we report previously unknown roles of the N-terminal domains of human Polλ for modulating its involvement in DNA damage tolerance and repair. By using Western blot analysis, fluorescence microscopy, and cell survival assays, we found that the BRCA1 C-terminal (BRCT) and proline/serine-rich (PSR) domains of Polλ affect its cellular localization and DNA damage responses. The nuclear localization signal (NLS) of Polλ was necessary to overcome the impediment of its nuclear localization caused by its BRCT and PSR domains. Induction of DNA damage resulted in recruitment of Polλ to chromatin, which was controlled by its BRCT and PSR domains. In addition, the presence of both domains was required for Polλ-mediated tolerance of oxidative DNA damage but not DNA methylation damage. These findings suggest that the N-terminal domains of Polλ are important for regulating its responses to DNA damage. |
| تدمد: | 1520-5010 0893-228X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7cadd1308435c09f096e5f286f48833 https://doi.org/10.1021/acs.chemrestox.7b00067 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d7cadd1308435c09f096e5f286f48833 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15205010 0893228X |
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