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Series GSE165647

Query DataSets for GSE165647

Status

Public on Jun 16, 2021

Title

CRY2 missense mutations suppress P53 and enhance cell growth

Organism

Experiment type

Expression profiling by high throughput sequencing

Summary

Disruption of circadian rhythms increases the risk of several types of cancer. Mammalian cryptochromes (CRY1 and CRY2) are circadian transcriptional repressors that are related to DNA repair enzymes. While CRYs lack DNA repair activity, they modulate the transcriptional response to DNA damage, and CRY2 can promote SCFFBXL3-mediated ubiquitination of c-MYC and other targets. Here, we characterize five mutations in CRY2 observed in human cancers in The Cancer Genome Atlas. We demonstrate that two orthologous mutations of mouse CRY2 (D325H and S510L) accelerate the growth of primary mouse fibroblasts expressing high levels of c-MYC. Neither mutant affects steady state levels of overexpressed c-MYC, and they have divergent impacts on circadian rhythms and on the ability of CRY2 to interact with SCFFBXL3. Unexpectedly, stable expression of either CRY2 D325H or of CRY2 S510L robustly suppresses P53 target gene expression, suggesting that this is the primary mechanism by which they influence cell growth.

Overall design

Comparisons of the transcriptomes of Cry2−/− mouse embryonic fibroblasts (MEFs) expressing c-MYC and WT or mutant Cry2 (D325H, S510L, or F428D), at low or high cell density.

Contributor(s)

Chan AB, Lamia K, Ibrahim LH, Bollong M

Citation(s)

Submission date

Jan 27, 2021

Last update date

Sep 15, 2021

Contact name

Lara Ibrahim

Organization name

Scripps Research

Street address

10550 N Torrey Pines Rd

City

San Diego

State/province

California

ZIP/Postal code

92037

Country

USA

Platforms (1)

BGISEQ-500 (Mus musculus)

Samples (30)

More...

GSM5047491	Sample 1: empty vector control; low density – Biological replicate 1
GSM5047492	Sample 2: empty vector control; low density – Biological replicate 2
GSM5047493	Sample 3: empty vector control; low density – Biological replicate 3

GSM5047494	Sample 4: CRY2; low density – Biological replicate 1
GSM5047495	Sample 5: CRY2; low density – Biological replicate 2
GSM5047496	Sample 6: CRY2; low density – Biological replicate 3
GSM5047497	Sample 7: CRY2 D325H; low density – Biological replicate 1
GSM5047498	Sample 8: CRY2 D325H; low density – Biological replicate 2
GSM5047499	Sample 9: CRY2 D325H; low density – Biological replicate 3
GSM5047500	Sample 10: CRY2 S510L; low density – Biological replicate 1
GSM5047501	Sample 11: CRY2 S510L; low density – Biological replicate 2
GSM5047502	Sample 12: CRY2 S510L; low density – Biological replicate 3
GSM5047503	Sample 13: CRY2 F428D; low density – Biological replicate 1
GSM5047504	Sample 14: CRY2 F428D; low density – Biological replicate 2
GSM5047505	Sample 15: CRY2 F428D; low density – Biological replicate 3
GSM5047506	Sample 16: empty vector control; high density – Biological replicate 1
GSM5047507	Sample 17: empty vector control; high density – Biological replicate 2
GSM5047508	Sample 18: empty vector control; high density – Biological replicate 3
GSM5047509	Sample 19: CRY2; high density – Biological replicate 1
GSM5047510	Sample 20: CRY2; high density – Biological replicate 2
GSM5047511	Sample 21: CRY2; high density – Biological replicate 3
GSM5047512	Sample 22: CRY2 D325H; high density – Biological replicate 1
GSM5047513	Sample 23: CRY2 D325H; high density – Biological replicate 2
GSM5047514	Sample 24: CRY2 D325H; high density – Biological replicate 3
GSM5047515	Sample 25: CRY2 S510L; high density – Biological replicate 1
GSM5047516	Sample 26: CRY2 S510L; high density – Biological replicate 2
GSM5047517	Sample 27: CRY2 S510L; high density – Biological replicate 3
GSM5047518	Sample 28: CRY2 F428D; high density – Biological replicate 1
GSM5047519	Sample 29: CRY2 F428D; high density – Biological replicate 2
GSM5047520	Sample 30: CRY2 F428D; high density – Biological replicate 3

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
GSE165647_chan.et.al.TPM.all.xlsx	7.8 Mb	(ftp)(http)	XLSX
SRA Run Selector
Raw data are available in SRA
Processed data are available on Series record

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