Stably transfected common fragile site sequences exhibit instability at ectopic sites
dc.contributor.author | Ragland, Ryan L. | en_US |
dc.contributor.author | Glynn, Michael W. | en_US |
dc.contributor.author | Arlt, Martin F. | en_US |
dc.contributor.author | Glover, Thomas W. | en_US |
dc.date.accessioned | 2008-08-27T20:04:45Z | |
dc.date.available | 2009-11-30T17:19:22Z | en_US |
dc.date.issued | 2008-10 | en_US |
dc.identifier.citation | Ragland, Ryan L.; Glynn, Michael W.; Arlt, Martin F.; Glover, Thomas W. (2008). "Stably transfected common fragile site sequences exhibit instability at ectopic sites." Genes, Chromosomes and Cancer 47(10): 860-872. <http://hdl.handle.net/2027.42/60903> | en_US |
dc.identifier.issn | 1045-2257 | en_US |
dc.identifier.issn | 1098-2264 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/60903 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18615677&dopt=citation | en_US |
dc.description.abstract | Common fragile sites (CFSs) are loci that are especially prone to forming gaps and breaks on metaphase chromosomes under conditions of replication stress. Although much has been learned about the cellular responses to gaps and breaks at CFSs, less is known about what makes these sites inherently unstable. CFS sequences are highly conserved in mammalian evolution and contain a number of sequence motifs that are hypothesized to contribute to their instability. To examine the role of CFS sequences in chromosome breakage, we stably transfected two BACs containing FRA3B sequences and two nonCFS control BACs containing similar sequence content into HCT116 cells and isolated cell clones with BACs integrated at ectopic sites. Integrated BACs were present at just a few to several hundred contiguous copies. Cell clones containing integrated FRA3B BACs showed a significant, three to sevenfold increase in aphidicolin-induced gaps and breaks at the integration site as compared to control BACs. Furthermore, many FRA3B integration sites displayed additional chromosome rearrangements associated with CFS instability. Clones were examined for replication timing and it was found that the integrated FRA3B sequences were not dependent on late replication for their fragility. This is the first direct evidence in human cells that introduction of CFS sequences into ectopic nonfragile loci is sufficient to recapitulate the instability found at CFSs. These data support the hypothesis that sequences at CFSs are inherently unstable, and are a major factor in the formation of replication stress induced gaps and breaks at CFSs. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 428580 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | Stably transfected common fragile site sequences exhibit instability at ectopic sites | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbsecondlevel | Oncology and Hematology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Human Genetics, University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Department of Human Genetics, University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Department of Human Genetics, University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Department of Human Genetics, University of Michigan, Ann Arbor, MI ; Department of Human Genetics 4909 Buhl, Box 5618, 1241 East Catherine Street, University of Michigan, Ann Arbor, Michigan 48109-0618, USA | en_US |
dc.identifier.pmid | 18615677 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/60903/1/20591_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/gcc.20591 | en_US |
dc.identifier.source | "Genes, Chromosomes and Cancer" | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.