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Series GSE33686 Query DataSets for GSE33686
Status Public on Jan 01, 2012
Title dNTP pools determine fork progression and origin usage under replication stress
Organism Saccharomyces cerevisiae
Experiment type Genome binding/occupancy profiling by genome tiling array
Summary Intracellular levels of deoxyribonucleoside triphosphate (dNTP) must be tightly regulated to preserve genome integrity. Indeed, alterations in dNTP pools have recently been associated with increased mutagenesis, genomic instability and tumorigenesis. However, the mechanisms by which low or imbalanced dNTP pools affect DNA replication remain poorly understood. Here, we have modulated the activity of ribonucleotide reductase (RNR), a key enzyme catalyzing a rate-limiting step of dNTP production, to monitor the effect of altered dNTP levels on replication dynamics in budding yeast. We show that dNTP pools are limiting for normal DNA synthesis as upregulation of RNR activity increases replication fork speed. In contrast, inhibition of RNR activity with hydroxyurea (HU) induces a sharp transition from a regular- to a slow-replication mode within minutes after S-phase entry. Interestingly, we found that upregulation of RNR activity delays this transition and that dNTP levels modulate both fork speed and origin usage under replication stress. Moreover, we report that chromosomal instability (CIN) mutants show increased dNTP pools and enhanced DNA synthesis in the presence of HU. Since upregulation of RNR allows forks to progress faster in the presence of DNA lesions, we propose that CIN mutants adapt to chronic replication stress by upregulating dNTP pools.
 
Overall design BrdU-IP from wild-type cells (30°C) and 12 mutant yeast cells. See Series GSE21014 for wild-type at 25°C and mutants already published in Crabbé et al. NSMB 2010
 
Contributor(s) Poli J, Tsaponina O, Crabbé L, Keszthelyi A, Pantesco V, Chabes A, Lengronne A, Pasero P
Citation(s) 22234185
Submission date Nov 14, 2011
Last update date Jan 09, 2016
Contact name Philippe Pasero
E-mail(s) ppasero@igh.cnrs.fr
Organization name Institute of Human Genetics - CNRS
Lab Pasero
Street address 141 rue de la Cardonille
City Montpellier
ZIP/Postal code 34396
Country France
 
Platforms (1)
GPL7250 [Sc03b_MR] Affymetrix GeneChip S. cerevisiae Tiling 1.0R Array
Samples (13)
GSM832840 asf1_BrdU_HU_60_min
GSM832841 ctf4_dun1_BrdU_HU_60_min
GSM832842 ctf4_rad9_BrdU_HU_60_min
Relations
BioProject PRJNA148291

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE33686_RAW.tar 1.4 Gb (http)(custom) TAR (of BAR, CEL)
Processed data provided as supplementary file

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