دورية أكاديمية
Selective Metal Ion Utilization Contributes to the Transformation of the Activity of Yeast Polymerase η from DNA Polymerization toward RNA Polymerization
العنوان: | Selective Metal Ion Utilization Contributes to the Transformation of the Activity of Yeast Polymerase η from DNA Polymerization toward RNA Polymerization |
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المؤلفون: | Eva Balint, Ildiko Unk |
المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 21, p 8248 (2020) |
بيانات النشر: | MDPI AG, 2020. |
سنة النشر: | 2020 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | polymerase η, enzyme kinetics, yeast, manganese, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | Polymerase eta (Polη) is a translesion synthesis DNA polymerase directly linked to cancer development. It can bypass several DNA lesions thereby rescuing DNA damage-stalled replication complexes. We previously presented evidence implicating Saccharomyces cerevisiae Polη in transcription elongation, and identified its specific RNA extension and translesion RNA synthetic activities. However, RNA synthesis by Polη proved rather inefficient under conditions optimal for DNA synthesis. Searching for factors that could enhance its RNA synthetic activity, we have identified the divalent cation of manganese. Here, we show that manganese triggers drastic changes in the activity of Polη. Kinetics experiments indicate that manganese increases the efficiency of ribonucleoside incorporation into RNA by ~400–2000-fold opposite undamaged DNA, and ~3000 and ~6000-fold opposite TT dimer and 8oxoG, respectively. Importantly, preference for the correct base is maintained with manganese during RNA synthesis. In contrast, activity is strongly impaired, and base discrimination is almost lost during DNA synthesis by Polη with manganese. Moreover, Polη shows strong preference for manganese during RNA synthesis even at a 25-fold excess magnesium concentration. Based on this, we suggest that a new regulatory mechanism, selective metal cofactor utilization, modulates the specificity of Polη helping it to perform distinct activities needed for its separate functions during replication and transcription. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1422-0067 1661-6596 |
العلاقة: | https://www.mdpi.com/1422-0067/21/21/8248Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test |
DOI: | 10.3390/ijms21218248 |
الوصول الحر: | https://doaj.org/article/e297ef3d348742e0978daca9a57dda70Test |
رقم الانضمام: | edsdoj.297ef3d348742e0978daca9a57dda70 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14220067 16616596 |
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DOI: | 10.3390/ijms21218248 |