2024-03-29T10:12:51Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1215542016-04-14T10:54:18Zcom_10261_134com_10261_1col_10261_387
Duch, Alba
Felipe-Abrio, Irene
Barroso, Sonia
Yaakov, Gilad
García-Rubio, María L.
Aguilera, Andrés
Posas, Francesc
2015-09-01T10:59:03Z
2015-09-01T10:59:03Z
2012-11-25
Nature 493(7430): 116-119 (2013)
0028-0836
http://hdl.handle.net/10261/121554
10.1038/nature11675
1476-4687
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100006373
http://dx.doi.org/10.13039/501100003741
http://dx.doi.org/10.13039/501100002809
Upon environmental changes or extracellular signals, cells are subjected
to marked changes in gene expression 1,2. Dealing with high
levels of transcription during replication is critical to prevent collisions
between the transcription and replication pathways and avoid
recombination events3–5. In response to osmostress, hundreds of
stress-responsive genes are rapidly induced by the stress-activated
protein kinase (SAPK) Hog1 (ref. 6), even during S phase7. Here we show in Saccharomyces cerevisae that a single signalling molecule, Hog1, coordinates both replication and transcription upon osmostress.
Hog1 interacts with and phosphorylates Mrc1, a component
of the replication complex8–11. Phosphorylation occurs at different
sites to those targeted by Mec1 upon DNA damage8,9. Mrc1 phosphorylation
by Hog1 delays early and late origin firing by preventing
Cdc45 loading, as well as slowing down replication-complex
progression. Regulation of Mrc1 by Hog1 is completely independent
of Mec1 and Rad53. Cells carrying a non-phosphorylatable
allele of MRC1 (mrc13A) do not delay replication upon stress and
show a marked increase in transcription-associated recombination,
genomic instability and Rad52 foci. In contrast, mrc13A induces
Rad53 and survivalin the presence of hydroxyurea or methylmethanesulphonate.
Therefore, Hog1 and Mrc1 define a novel S-phase
checkpoint independent of the DNA-damage checkpoint that permits
eukaryotic cells to prevent conflicts between DNA replication
and transcription, which would otherwise lead to genomic instability
when both phenomena are temporally coincident.
eng
closedAccess
DNA damage checkpoints
DNA replication
Transcription
Cell biology
Coordinated control of replication and transcription by a SAPK protects genomic integrity
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