Linked Life Data

19465922

Source:http://linkedlifedata.com/resource/pubmed/id/19465922

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-6-8
pubmed:abstractText
Several inherited syndromes in humans are associated with cancer predisposition. The gene products defective in two of these disorders, BLM (a helicase defective in Bloom's syndrome) and FANC A-N (defective in Fanconi anaemia), associate in a multienzyme complex called BRAFT. How these proteins suppress tumorigenesis remains unclear, although both conditions are associated with chromosome instability. Here we show that the Fanconi anaemia proteins FANCD2 and FANCI specifically associate with common fragile site loci irrespective of whether the chromosome is broken. Unexpectedly, these loci are frequently interlinked through BLM-associated ultra-fine DNA bridges (UFBs) even as cells traverse mitosis. Similarly to fragile site expression, fragile site bridging is induced after partial inhibition of DNA replication. We propose that, after replication stress, sister chromatids are interlinked by replication intermediates primarily at genetic loci with intrinsic replication difficulties, such as fragile sites. In Bloom's syndrome cells, inefficient resolution of DNA linkages at fragile sites gives rise to increased numbers of anaphase UFBs and micronuclei containing fragile site DNA. Our data have general implications concerning the contribution of fragile site loci to chromosomal instability and tumorigenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-4679
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
753-60
pubmed:meshHeading
pubmed-meshheading:19465922-Acid Anhydride Hydrolases, pubmed-meshheading:19465922-Bloom Syndrome, pubmed-meshheading:19465922-Cell Line, pubmed-meshheading:19465922-Chromatids, pubmed-meshheading:19465922-Chromosome Fragile Sites, pubmed-meshheading:19465922-Chromosome Mapping, pubmed-meshheading:19465922-DNA Replication, pubmed-meshheading:19465922-Fanconi Anemia, pubmed-meshheading:19465922-Fanconi Anemia Complementation Group D2 Protein, pubmed-meshheading:19465922-Fanconi Anemia Complementation Group Proteins, pubmed-meshheading:19465922-Humans, pubmed-meshheading:19465922-In Situ Hybridization, Fluorescence, pubmed-meshheading:19465922-Mitosis, pubmed-meshheading:19465922-Neoplasm Proteins, pubmed-meshheading:19465922-Nucleic Acid Conformation, pubmed-meshheading:19465922-RNA Interference, pubmed-meshheading:19465922-RecQ Helicases
pubmed:year
2009
pubmed:articleTitle
Replication stress induces sister-chromatid bridging at fragile site loci in mitosis.
pubmed:affiliation
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't