Translesion synthesis DNA polymerase η exhibits a specific RNA extension activity and a transcription-associated function

Vamsi K Gali, Eva Balint, Nataliia Serbyn, Orsolya Frittmann, Francoise Stutz, Ildiko Unk

Research output: Contribution to journalArticle

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4 Downloads (Pure)

Abstract

Polymerase eta (Polη) is a low fidelity translesion synthesis DNA polymerase that rescues damage-stalled replication by inserting deoxy-ribonucleotides opposite DNA damage sites resulting in error-free or mutagenic damage bypass. In this study we identify a new specific RNA extension activity of Polη of Saccharomyces cerevisiae. We show that Polη is able to extend RNA primers in the presence of ribonucleotides (rNTPs), and that these reactions are an order of magnitude more efficient than the misinsertion of rNTPs into DNA. Moreover, during RNA extension Polη performs error-free bypass of the 8-oxoguanine and thymine dimer DNA lesions, though with a 10(3) and 10(2)-fold lower efficiency, respectively, than it synthesizes opposite undamaged nucleotides. Furthermore, in vivo experiments demonstrate that the transcription of several genes is affected by the lack of Polη, and that Polη is enriched over actively transcribed regions. Moreover, inactivation of its polymerase activity causes similar transcription inhibition as the absence of Polη. In summary, these results suggest that the new RNA synthetic activity of Polη can have in vivo relevance.

Original languageEnglish
Article number13055
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 12 Oct 2017

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DNA-Directed DNA Polymerase
Ribonucleotides
RNA
Pyrimidine Dimers
DNA
DNA Damage
Saccharomyces cerevisiae
Nucleotides
Genes

Keywords

  • Journal Article
  • Transcriptional regulatory elements
  • translesion synthesis

Cite this

Translesion synthesis DNA polymerase η exhibits a specific RNA extension activity and a transcription-associated function. / Gali, Vamsi K; Balint, Eva; Serbyn, Nataliia; Frittmann, Orsolya; Stutz, Francoise; Unk, Ildiko.

In: Scientific Reports, Vol. 7, 13055, 12.10.2017.

Research output: Contribution to journalArticle

Gali, Vamsi K ; Balint, Eva ; Serbyn, Nataliia ; Frittmann, Orsolya ; Stutz, Francoise ; Unk, Ildiko. / Translesion synthesis DNA polymerase η exhibits a specific RNA extension activity and a transcription-associated function. In: Scientific Reports. 2017 ; Vol. 7.
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abstract = "Polymerase eta (Polη) is a low fidelity translesion synthesis DNA polymerase that rescues damage-stalled replication by inserting deoxy-ribonucleotides opposite DNA damage sites resulting in error-free or mutagenic damage bypass. In this study we identify a new specific RNA extension activity of Polη of Saccharomyces cerevisiae. We show that Polη is able to extend RNA primers in the presence of ribonucleotides (rNTPs), and that these reactions are an order of magnitude more efficient than the misinsertion of rNTPs into DNA. Moreover, during RNA extension Polη performs error-free bypass of the 8-oxoguanine and thymine dimer DNA lesions, though with a 10(3) and 10(2)-fold lower efficiency, respectively, than it synthesizes opposite undamaged nucleotides. Furthermore, in vivo experiments demonstrate that the transcription of several genes is affected by the lack of Polη, and that Polη is enriched over actively transcribed regions. Moreover, inactivation of its polymerase activity causes similar transcription inhibition as the absence of Polη. In summary, these results suggest that the new RNA synthetic activity of Polη can have in vivo relevance.",
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AU - Balint, Eva

AU - Serbyn, Nataliia

AU - Frittmann, Orsolya

AU - Stutz, Francoise

AU - Unk, Ildiko

N1 - We thank Andres Aguilera for providing the pCYC-LacZ plasmid for the GLRO experiments, and Szilvia Minorits for technical assistance. This work was also supported by grants from the National Research, Development and Innovation Office: GINOP-2.3.2-15-2016-00001 and GINOP-2.3.2-15-2016-00024.

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N2 - Polymerase eta (Polη) is a low fidelity translesion synthesis DNA polymerase that rescues damage-stalled replication by inserting deoxy-ribonucleotides opposite DNA damage sites resulting in error-free or mutagenic damage bypass. In this study we identify a new specific RNA extension activity of Polη of Saccharomyces cerevisiae. We show that Polη is able to extend RNA primers in the presence of ribonucleotides (rNTPs), and that these reactions are an order of magnitude more efficient than the misinsertion of rNTPs into DNA. Moreover, during RNA extension Polη performs error-free bypass of the 8-oxoguanine and thymine dimer DNA lesions, though with a 10(3) and 10(2)-fold lower efficiency, respectively, than it synthesizes opposite undamaged nucleotides. Furthermore, in vivo experiments demonstrate that the transcription of several genes is affected by the lack of Polη, and that Polη is enriched over actively transcribed regions. Moreover, inactivation of its polymerase activity causes similar transcription inhibition as the absence of Polη. In summary, these results suggest that the new RNA synthetic activity of Polη can have in vivo relevance.

AB - Polymerase eta (Polη) is a low fidelity translesion synthesis DNA polymerase that rescues damage-stalled replication by inserting deoxy-ribonucleotides opposite DNA damage sites resulting in error-free or mutagenic damage bypass. In this study we identify a new specific RNA extension activity of Polη of Saccharomyces cerevisiae. We show that Polη is able to extend RNA primers in the presence of ribonucleotides (rNTPs), and that these reactions are an order of magnitude more efficient than the misinsertion of rNTPs into DNA. Moreover, during RNA extension Polη performs error-free bypass of the 8-oxoguanine and thymine dimer DNA lesions, though with a 10(3) and 10(2)-fold lower efficiency, respectively, than it synthesizes opposite undamaged nucleotides. Furthermore, in vivo experiments demonstrate that the transcription of several genes is affected by the lack of Polη, and that Polη is enriched over actively transcribed regions. Moreover, inactivation of its polymerase activity causes similar transcription inhibition as the absence of Polη. In summary, these results suggest that the new RNA synthetic activity of Polη can have in vivo relevance.

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