| RRC ID |
73342
|
| 著者 |
Duch A, Canal B, Barroso SI, García-Rubio M, Seisenbacher G, Aguilera A, de Nadal E, Posas F.
|
| タイトル |
Multiple signaling kinases target Mrc1 to prevent genomic instability triggered by transcription-replication conflicts.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Conflicts between replication and transcription machineries represent a major source of genomic instability and cells have evolved strategies to prevent such conflicts. However, little is known regarding how cells cope with sudden increases of transcription while replicating. Here, we report the existence of a general mechanism for the protection of genomic integrity upon transcriptional outbursts in S phase that is mediated by Mrc1. The N-terminal phosphorylation of Mrc1 blocked replication and prevented transcription-associated recombination (TAR) and genomic instability during stress-induced gene expression in S phase. An unbiased kinome screening identified several kinases that phosphorylate Mrc1 at the N terminus upon different environmental stresses. Mrc1 function was not restricted to environmental cues but was also required when unscheduled transcription was triggered by low fitness states such as genomic instability or slow growth. Our data indicate that Mrc1 integrates multiple signals, thereby defining a general safeguard mechanism to protect genomic integrity upon transcriptional outbursts.
|
| 巻・号 |
9(1)
|
| ページ |
379
|
| 公開日 |
2018-1-25
|
| DOI |
10.1038/s41467-017-02756-x
|
| PII |
10.1038/s41467-017-02756-x
|
| PMID |
29371596
|
| PMC |
PMC5785523
|
| MeSH |
Cell Cycle Proteins / genetics*
Cell Cycle Proteins / metabolism
DNA Replication*
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression Regulation, Fungal*
Genomic Instability*
Glucose / deficiency
Hot Temperature
Hydrogen Peroxide / pharmacology
Osmotic Pressure
Oxidative Stress / genetics
Phosphorylation
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
S Phase
Saccharomyces cerevisiae / drug effects
Saccharomyces cerevisiae / genetics*
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / genetics*
Saccharomyces cerevisiae Proteins / metabolism
Signal Transduction
Sodium Chloride / pharmacology
Transcription, Genetic*
|
| IF |
12.121
|
| リソース情報 |
| 酵母 |
pNHK53, pMK152 |
