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Series GSE180530 Query DataSets for GSE180530
Status Public on Jul 01, 2023
Title Palbociclib interferes with origin firing in a pRb independent manner
Organism Homo sapiens
Experiment type Genome variation profiling by genome tiling array
Summary Over the last decade, CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have emerged as promising anticancer drugs. Numerous studies have demonstrated that CDK4/6 inhibitors efficiently block the pRb-E2F pathway and induce cell cycle arrest in pRb-proficient cells. Based on these studies, the inhibitors have been approved by the FDA for treatment of advanced hormonal receptor (HR) positive breast cancers in combination with hormonal therapy. However, some evidence has recently shown unexpected effects of the inhibitors, promoting needs to understand more about the mechanism of inhibitors beyond pRb. Our study demonstrates here for the first time how palbociclib impairs the origin firing in the DNA replication process in pRb-deficient cell lines. Strikingly, despite the absence of pRb, cells treated with palbociclib synthesize less DNA without any induced cell cycle arrest. Furthermore, palbociclib treatment disturbs the temporal program of DNA replication and reduces the density of replication forks. Cells treated with palbociclib show a defect in the loading of proteins of the Pre-initiation complex (Pre-IC) on chromatin, indicating a reduced initiation of DNA replication. Our findings highlight hidden effects of palbociclib on the dynamics of DNA replication and on its cytotoxic consequences on cell viability in the absence of pRb. This study provides a potential therapeutic application of palbociclib to target genomic instability towards pRb deficient patient
Overall design nascent-DNA from early S-phase versus nascent-DNA from late S-phase
Contributor(s) Kim S, Koudrioukoff S, Jean-Charles Cadoret CM
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Submission date Jul 21, 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 (10)
GSM5464398 NCI treated with DMSO replicate 1
GSM5464399 NCI treated with DMSO replicate 2
GSM5464400 NCI treated with Ribociclib replicate 1
BioProject PRJNA748597

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE180530_RAW.tar 520.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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