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Series GSE172417

Query DataSets for GSE172417

Status

Public on Jun 01, 2021

Title

DYNAMICS OF REPLICATION ORIGIN OVER-ACTIVATION

Organism

Experiment type

Genome binding/occupancy profiling by high throughput sequencing
Other

Summary

Safeguards against excess DNA replication are often dysregulated in cancer, and driving cancer cells towards over-replication is a promising therapeutic strategy. We determined DNA synthesis patterns in cancer cells undergoing partial genome re-replication due to perturbed regulatory interactions ("re-replicating cells"). These cells exhibited slow replication, increased frequency of replication initiation events and a skewed initiation pattern that preferentially reactivated early-replicating origins. Unlike in cells exposed to replication stress, which activated a novel group of hitherto unutilized (”dormant”) replication origins, the preferred re-replicating origins arose from the same pool of potential origins as those activated during normal growth. Mechanistically, the skewed initiation pattern reflected a disproportionate distribution of pre-replication complexes on distinct regions of licensed chromatin prior to replication. This distinct pattern suggests that circumventing the strong inhibitory interactions that normally prevent excess DNA synthesis can occur via at least two pathways, each activating a distinct set of replication origins.

Overall design

Nascent strands were purified with the lambda exonuclease methods from HCT116 cells or U2OS. Re-replicated DNA was isolated by BrdU cesium chloride gradient. Chromatin from HCT116 cells was subjected to ChIP-Seq with antibody directed against CDT1 and pS139-MCM2.

Contributor(s)

Citation(s)

Submission date

Apr 20, 2021

Last update date

Jul 21, 2021

Contact name

Christophe E Redon

E-mail(s)

redonc@mail.nih.gov

Phone

240-760-7338

Organization name

NIH

Street address

37 Convent Drive

City

Bethesda

State/province

MD

ZIP/Postal code

20892

Country

USA

Platforms (3)

GPL18573	Illumina NextSeq 500 (Homo sapiens)
GPL20301	Illumina HiSeq 4000 (Homo sapiens)
GPL24676	Illumina NovaSeq 6000 (Homo sapiens)

Samples (38)

More...

GSM5255581	HCT116 HH Control (Genomic DNA with BrdU incoprated)
GSM5255582	HCT116 MLN4924 200 nM (Re-replicated DNA)
GSM5255583	HCT116 MLN4924 400 nM (Re-replicated DNA)

GSM5255584	HCT116 control genomic DNA for HCT116 control HL (Genomic DNA)
GSM5255585	HCT116 MLN4924 genomic DNA for HCT116 MLN4924 HL& HH (Genomic DNA)
GSM5255586	HCT116 control HL (Nascent strands)
GSM5255587	HCT116 MLN4924 HL (Nascent strands)
GSM5255588	HCT116 MLN4924 HH (Nascent strands)
GSM5255589	HCT116 Control 30h (Nascent strands)
GSM5255590	HCT116 Control 45h (Nascent strands)
GSM5255591	HCT116 MLN4924 30h (Nascent strands)
GSM5255592	HCT116 MLN4924 45h (Nascent strands)
GSM5255593	HCT116 genomic DNA for 30h&45h both control &MLN4924
GSM5255594	HCT116 G1 input for HCT116 G1 CDT1 (input DNA)
GSM5255595	HCT116 MS input for HCT116 MS CDT1 (input DNA)
GSM5255596	HCT116 G1 CDT1 Replicate 1 (ChIPSeq)
GSM5255597	HCT116 G1 CDT1 Replicate 2 (ChIPSeq)
GSM5255598	HCT116 MS CDT1 Replicate 1 (ChIPSeq)
GSM5255599	HCT116 MS CDT1 Replicate 2 (ChIPSeq)
GSM5255600	HCT116 input for HCT116 control CDT1 and p139-MCM2-1&2 (input DNA)
GSM5255601	HCT116 input for HCT116 re-replication CDT1 and p139-MCM2-1&2 (input DNA)
GSM5255602	HCT116 control CDT1 Replicate 1 (ChIPSeq)
GSM5255603	HCT116 control CDT1 Replicate 2 (ChIPSeq)
GSM5255604	HCT116 Re-replication CDT1 Replicate 1 (ChIPSeq)
GSM5255605	HCT116 Re-replication CDT1 Replicate 2 (ChIPSeq)
GSM5255606	HCT116 control p139-MCM2 Replicate 1 (ChIPSeq)
GSM5255607	HCT116 control p139-MCM2 Replicate 2 (ChIPSeq)
GSM5255608	HCT116 Re-replication p139-MCM2 Replicate 1 (ChIPSeq)
GSM5255609	HCT116 Re-replication p139-MCM2 Replicate 2 (ChIPSeq)
GSM5255610	HCT116 DNA from G1 cells for timing (genomic DNA)
GSM5255611	HCT116 DNA from normal replicating cells for timing (genomic DNA)
GSM5255612	HCT116 DNA from re-replicating cells for timing (genomic DNA)
GSM5255613	U2OS CDT1OE control Replicate 1 (Nascent strands)
GSM5255614	U2OS CDT1OE control Replicate 2 (Nascent strands)
GSM5255615	U2OS CDT1OE doxcycline Replicate 1 (Nascent strands)
GSM5255616	U2OS CDT1OE doxcycline Replicate 2 (Nascent strands)
GSM5255617	U2OS CDT1OE conntrol genomic DNA for U2OS CDT1OE control 1&2
GSM5255618	U2OS CDT1OE doxcycyclinne genomic DNA for U2OS CDT1OE control 1&2

Relations

BioProject

SRA

Download family	Format
SOFT formatted family file(s)	SOFT
MINiML formatted family file(s)	MINiML
Series Matrix File(s)	TXT

Supplementary file	Size	Download	File type/resource
GSE172417_RAW.tar	3.2 Gb	(http)(custom)	TAR (of BED, BROADPEAK, BW)
SRA Run Selector
Raw data are available in SRA
Processed data provided as supplementary file

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