The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ
Abstract PCNA is a central orchestrator of cellular processes linked to DNA metabolism. It is a binding platform for a plethora of proteins and coordinates and regulates the activity of several pathways. The outer side of PCNA comprises most of the known interacting and regulatory surfaces, whereas...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-09208-7 |
| _version_ | 1811332110594605056 |
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| author | Robert Toth Miklos Halmai Zsuzsanna Gyorfy Eva Balint Ildiko Unk |
| author_facet | Robert Toth Miklos Halmai Zsuzsanna Gyorfy Eva Balint Ildiko Unk |
| author_sort | Robert Toth |
| collection | DOAJ |
| description | Abstract PCNA is a central orchestrator of cellular processes linked to DNA metabolism. It is a binding platform for a plethora of proteins and coordinates and regulates the activity of several pathways. The outer side of PCNA comprises most of the known interacting and regulatory surfaces, whereas the residues at the inner side constitute the sliding surface facing the DNA double helix. Here, by investigating the L154A mutation found at the inner side, we show that the inner surface mediates protein interactions essential for genome stability. It forms part of the binding site of Rad18, a key regulator of DNA damage tolerance, and is required for PCNA sumoylation which prevents unscheduled recombination during replication. In addition, the L154 residue is necessary for stable complex formation between PCNA and the replicative DNA polymerase δ. Hence, its absence increases the mutation burden of yeast cells due to faulty replication. In summary, the essential role of the L154 of PCNA in guarding and maintaining stable replication and promoting DNA damage tolerance reveals a new connection between these processes and assigns a new coordinating function to the central channel of PCNA. |
| first_indexed | 2024-04-13T16:31:46Z |
| format | Article |
| id | doaj.art-d0a329c062004f91985dbabf9e00435b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T16:31:46Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d0a329c062004f91985dbabf9e00435b2022-12-22T02:39:33ZengNature PortfolioScientific Reports2045-23222022-03-0112111310.1038/s41598-022-09208-7The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δRobert Toth0Miklos Halmai1Zsuzsanna Gyorfy2Eva Balint3Ildiko Unk4The Institute of Genetics, Biological Research Centre, Szeged, Eotvos Loránd Research NetworkThe Institute of Genetics, Biological Research Centre, Szeged, Eotvos Loránd Research NetworkThe Institute of Genetics, Biological Research Centre, Szeged, Eotvos Loránd Research NetworkThe Institute of Genetics, Biological Research Centre, Szeged, Eotvos Loránd Research NetworkThe Institute of Genetics, Biological Research Centre, Szeged, Eotvos Loránd Research NetworkAbstract PCNA is a central orchestrator of cellular processes linked to DNA metabolism. It is a binding platform for a plethora of proteins and coordinates and regulates the activity of several pathways. The outer side of PCNA comprises most of the known interacting and regulatory surfaces, whereas the residues at the inner side constitute the sliding surface facing the DNA double helix. Here, by investigating the L154A mutation found at the inner side, we show that the inner surface mediates protein interactions essential for genome stability. It forms part of the binding site of Rad18, a key regulator of DNA damage tolerance, and is required for PCNA sumoylation which prevents unscheduled recombination during replication. In addition, the L154 residue is necessary for stable complex formation between PCNA and the replicative DNA polymerase δ. Hence, its absence increases the mutation burden of yeast cells due to faulty replication. In summary, the essential role of the L154 of PCNA in guarding and maintaining stable replication and promoting DNA damage tolerance reveals a new connection between these processes and assigns a new coordinating function to the central channel of PCNA.https://doi.org/10.1038/s41598-022-09208-7 |
| spellingShingle | Robert Toth Miklos Halmai Zsuzsanna Gyorfy Eva Balint Ildiko Unk The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ Scientific Reports |
| title | The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ |
| title_full | The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ |
| title_fullStr | The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ |
| title_full_unstemmed | The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ |
| title_short | The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ |
| title_sort | inner side of yeast pcna contributes to genome stability by mediating interactions with rad18 and the replicative dna polymerase δ |
| url | https://doi.org/10.1038/s41598-022-09208-7 |
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