Chl1 helicase controls replication fork progression by regulating dNTP pools
| Autor: | Amandine Batté, Sophie C van der Horst, Mireille Tittel-Elmer, Su Ming Sun, Sushma Sharma, Jolanda van Leeuwen, Andrei Chabes, Haico van Attikum |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
DNA Replication
Saccharomyces cerevisiae Proteins Ecology Chromosomal Proteins Non-Histone Health Toxicology and Mutagenesis Cell- och molekylärbiologi Deoxyribonucleotides DNA Helicases Cell Cycle Proteins Plant Science Biochemistry Genetics and Molecular Biology (miscellaneous) DEAD-box RNA Helicases enzymes and coenzymes (carbohydrates) Humans Cell Cycle Proteins/genetics Cells Cultured Chromosomal Proteins Non-Histone/genetics DNA Replication/genetics Deoxyribonucleotides/genetics Deoxyribonucleotides/metabolism Saccharomyces cerevisiae Proteins/genetics Research Articles Cell and Molecular Biology Research Article |
| Zdroj: | Life Science Alliance, 5(4). LIFE SCIENCE ALLIANCE LLC Life science alliance, vol. 5, no. 4, pp. e202101153 Life Science Alliance Life Science Alliance, 5(4) |
| Popis: | Chl1 helicase affects RPA-dependent checkpoint activation after replication fork arrest by ensuring proper dNTP levels, thereby controlling replication fork progression under stress conditions. Eukaryotic cells have evolved a replication stress response that helps to overcome stalled/collapsed replication forks and ensure proper DNA replication. The replication checkpoint protein Mrc1 plays important roles in these processes, although its functional interactions are not fully understood. Here, we show that MRC1 negatively interacts with CHL1, which encodes the helicase protein Chl1, suggesting distinct roles for these factors during the replication stress response. Indeed, whereas Mrc1 is known to facilitate the restart of stalled replication forks, we uncovered that Chl1 controls replication fork rate under replication stress conditions. Chl1 loss leads to increased RNR1 gene expression and dNTP levels at the onset of S phase likely without activating the DNA damage response. This in turn impairs the formation of RPA-coated ssDNA and subsequent checkpoint activation. Thus, the Chl1 helicase affects RPA-dependent checkpoint activation in response to replication fork arrest by ensuring proper intracellular dNTP levels, thereby controlling replication fork progression under replication stress conditions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|