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Series GSE180865 Query DataSets for GSE180865
Status Public on Jul 01, 2023
Title GNL3/nucleostemin links DNA replication homeostasis and replication forks stability
Organism Homo sapiens
Experiment type Genome variation profiling by array
Summary The regulation of replication forks stalling and replication origins firing must be tightly coordinated to prevents genomic instability. Here we show that GNL3/nucleostemin, a GTP-binding protein able to shuttle between the nucleolus and the nucleoplasm, limits replicative stress by limiting replication origins firing. GNL3 is in proximity of nascent DNA and its depletion reduces forks speed but increases forks density and replication origins firing. When subjected to exogenous replicative stress, cells impaired for GNL3 exhibits MRN-dependent resection and RPA phosphorylation.  Strikingly, inhibition of origin firing using CDC7 inhibitor decreased resection in absence of GNL3 but not in absence of BRCA1, suggesting that GNL3 does not protect nascent strand directly from resection. Consistent with this, overexpression of GNL3 leads to an increased resection in response to replicative stress and enhanced origin firing efficiency. These data indicate that the probability of origins firing is tightly regulated by GNL3 to limit replicative stress. Finally, we show that ORC2 and GNL3 interacts together in the nucleolus. We propose a model where GNL3 level is crucial to determine the correct amount of ORC2 on chromatin by sequestrating it in the nucleolus thanks to the capacity of GNL3 to shuttle between nucleoplasm and nucleolus.
Overall design nascent-DNA from early S-phase versus nascent-DNA from late S-phase
Contributor(s) Lebdy R, Canut M, Patouillard J, Cadoret J, Letessier A, Basbous J, Miotto B, Constantinou A, Abou-Merhi R, Ribeyre C
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Submission date Jul 26, 2021
Last update date Jul 03, 2023
Contact name Jean-Charles Cadoret
Organization name CNRS/ Université de Paris
Street address 15 rue hélène Brion
City Paris
ZIP/Postal code 75013
Country France
Platforms (1)
GPL10123 Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version)
Samples (6)
GSM5473832 HeLa-S3 siControl_1
GSM5473833 HeLa-S3 siControl_2
GSM5473834 HeLa-S3 siRif1_1
BioProject PRJNA749783

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Supplementary file Size Download File type/resource
GSE180865_RAW.tar 312.5 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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