GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE103624 Query DataSets for GSE103624
Status Public on Nov 23, 2017
Title BRCA1 suppresses microhomology-mediated tandem duplications at Tus/Ter-stalled replication forks
Organism Mus musculus
Experiment type Other
Summary Small ~10 kb microhomology-mediated tandem duplications (“Group 1 TDs”) are abundant in BRCA1-linked but not BRCA2-linked breast cancer genomes. Here, we define the mechanism underlying this rearrangement signature. We show that BRCA1, but not BRCA2, suppresses TDs at a Tus/Ter site-specific chromosomal replication fork barrier in primary mammalian cells. BRCA1 has no equivalent role at chromosomal double strand breaks, indicating specificity for the stalled fork response. Two motor proteins—FANCM and the Bloom’s syndrome helicase—suppress Tus/Ter-induced TDs in BRCA1 mutants, revealing the existence of a multi-gene TD suppressor network. TDs arise by a “replication restart-bypass” mechanism terminated by end joining or microhomology-mediated template switching, the latter forming complex TD breakpoints. We show that solitary DNA ends form directly at Tus/Ter, implicating misrepair of these lesions in TD formation. We find that BRCA1 inactivation is strongly associated with Group 1 TDs in ovarian cancer. The Group 1 TD phenotype may be a general signature of BRCA1-deficient cancer
Overall design LAM-HTGTS from a Cas9/gRNA bait DSB 30kb away from the 1xGFP Ter array cassette inserted in the ROSA26 locus
Contributor(s) Willis NA, Frock RL, Alt FW, Scully R
Citation(s) 29168504
Submission date Sep 08, 2017
Last update date May 15, 2019
Contact name Richard L Frock
Organization name Stanford University
Department Radiation Oncology
Lab Frock Lab
Street address 269 Campus Drive
City Stanford
State/province California
ZIP/Postal code 94305
Country USA
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (25)
GSM2776852 EV_BRCA1del_siFANCM_Rep1
GSM2776853 EV_BRCA1del_siFANCM_Rep2
GSM2776854 ISceI_BRCA1del_siFANCM_Rep1
BioProject PRJNA403795
SRA SRP117142

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

Supplementary file Size Download File type/resource
GSE103624_EV_BRCA1del_siFANCM_s2.txt.gz 12.5 Kb (ftp)(http) TXT
GSE103624_ISceI_BRCA1del_siFANCM_s2.txt.gz 49.4 Kb (ftp)(http) TXT
GSE103624_Tus_BRCA1del_siBLM_s3.txt.gz 42.5 Kb (ftp)(http) TXT
GSE103624_Tus_BRCA1del_siBRCA1_s3.txt.gz 41.0 Kb (ftp)(http) TXT
GSE103624_Tus_BRCA1del_siFANCM_s3.txt.gz 42.9 Kb (ftp)(http) TXT
GSE103624_Tus_BRCA1del_siLuciferase_s3.txt.gz 43.7 Kb (ftp)(http) TXT
GSE103624_Tus_BRCA1flox_siBLM_s2.txt.gz 29.6 Kb (ftp)(http) TXT
GSE103624_Tus_BRCA1flox_siBRCA1_s2.txt.gz 28.2 Kb (ftp)(http) TXT
GSE103624_Tus_BRCA1flox_siFANCM_s3.txt.gz 43.9 Kb (ftp)(http) TXT
GSE103624_Tus_BRCA1flox_siLuciferase_s2.txt.gz 38.7 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap