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Series GSE55420 Query DataSets for GSE55420
Status Public on Mar 15, 2014
Title Regulatory Mechanisms That Prevent Re-initiation of DNA Replication Can Be Locally Modulated at Origins by Nearby Sequence Elements
Organism Saccharomyces cerevisiae
Experiment type Genome variation profiling by genome tiling array
Summary Eukaryotic cells must inhibit re-initiation of DNA replication at each of the thousands of origins in their genome because re-initiation can generate genomic alterations with extraordinary frequency. To minimize the probability of re-initiation from so many origins, cells use a battery of regulatory mechanisms that reduce the activity of replication initiation proteins. Given the global nature of these mechanisms, it has been presumed that all origins are inhibited identically. However, origins re-initiate with diverse efficiencies when these mechanisms are disabled, and this diversity cannot be explained by differences in the efficiency or timing of origin initiation during normal S phase replication. This observation raises the possibility of an additional layer of replication control that can differentially regulate re-initiation at distinct origins. We have identified novel genetic elements that are necessary for preferential re-initiation of two origins and sufficient to confer preferential re-initiation on heterologous origins when the control of re-initiation is partially deregulated. The elements do not enhance the S phase timing or efficiency of adjacent origins and thus are specifically acting as re-initiation promoters (RIPs). We have mapped the two RIPs to ~60 bp AT rich sequences that act in a distance- and sequence-dependent manner. During the induction of re-replication, Mcm2-7 reassociates both with origins that preferentially re-initiate and origins that do not, suggesting that the RIP elements can overcome a block to re-initiation imposed after Mcm2-7 associates with origins. Our findings identify a local level of control in the block to re-initiation. This local control creates a complex genomic landscape of re-replication potential that is revealed when global mechanisms preventing re-replication are compromised. Hence, if re-replication does contribute to genomic alterations, as has been speculated for cancer cells, some regions of the genome may be more susceptible to these alterations than others.
 
Overall design 142 array CGH experiments are presented. Each experiment is done in experimental replicate.
Cells grown as described in Richardson CD and Li JJ PLoS Genetics 2014. Ch1 samples taken from replicating (S phase) or re-replicating (M phase + 3/6 hour induced). Ch2 samples taken from M phase arrested DNA.
 
Citation(s) 24945837
Submission date Feb 27, 2014
Last update date Sep 09, 2014
Contact name Chris Richardson
E-mail(s) [email protected]
Organization name UCSB
Department Molecular, Cellular, and Developmental Biology
Street address UCSB
City Santa Barbara
State/province CA
ZIP/Postal code 93106-9625
Country USA
 
Platforms (1)
GPL3412 Li UCSF yeast 14062 v1.0
Samples (282)
GSM1335863 MC2A-ARS317-YJL8923-rerep3hr
GSM1335864 MC2A-ARS317-YJL8924-rerep3hr
GSM1335865 MC2Ao-1238(+133to-100)-YJL9566-rerep6hr
Relations
BioProject PRJNA239546

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

Supplementary file Size Download File type/resource
GSE55420_RAW.tar 384.7 Mb (http)(custom) TAR (of GPR)
Processed data included within Sample table

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