Cancer predisposition caused by elevated mitotic recombination in Bloom mice

@article{Luo2000CancerPC,
  title={Cancer predisposition caused by elevated mitotic recombination in Bloom mice},
  author={Guangbin Luo and Irma M. Santoro and Lisa D. McDaniel and Ichiko Nishijima and Michael Mills and Hagop Youssoufian and Hannes Vogel and Roger A. Schultz and Allan Bradley},
  journal={Nature Genetics},
  year={2000},
  volume={26},
  pages={424-429}
}
Bloom syndrome is a disorder associated with genomic instability that causes affected people to be prone to cancer. Bloom cell lines show increased sister chromatid exchange, yet are proficient in the repair of various DNA lesions. The underlying cause of this disease are mutations in a gene encoding a RECQ DNA helicase. Using embryonic stem cell technology, we have generated viable Bloom mice that are prone to a wide variety of cancers. Cell lines from these mice show elevations in the rates… 
Enhanced Tumor Formation in Mice Heterozygous for Blm Mutation
TLDR
Observations indicate that Blmis a modifier of tumor formation in the mouse and that Blmhaploinsufficiency is associated with tumor predisposition, a finding with important implications for cancer risk in humans.
Mutation of the Murine Bloom's Syndrome Gene Produces Global Genome Destabilization
TLDR
Results show that Blm gene mutation produces chromosomal instability, strengthening a role for CIN in the development of human cancer.
Hyper-recombination and genetic instability in BLM-deficient epithelial cells.
TLDR
Surprisingly, BLM-deficient colorectal cancer epithelial cells did not display gross chromosomal rearrangements nor a change in the rates of chromosome gains and losses, however, the enhanced homologous recombination was associated with losses of heterozygosity.
Enhancement of microhomology-mediated genomic rearrangements by transient loss of mouse Bloom syndrome helicase.
TLDR
The experimental approach successfully uncovered the detailed molecular mechanisms of as-yet-uncharacterized loss of heterozygosities and reveals the significant contribution of microhomology-mediated genomic rearrangements, which could be widely applicable to the early steps of cancer formation in general.
Genomic instability and cancer: lessons from analysis of Bloom's syndrome.
TLDR
The present article begins by introducing BLM and its binding partners before reviewing its known biochemical activities and its potential roles both as a pro-recombinase and as a suppressor of homologous recombination.
Defective sister-chromatid cohesion, aneuploidy and cancer predisposition in a mouse model of type II Rothmund-Thomson syndrome.
TLDR
Observations provide evidence for a previously unsuspected role for Recql4 in sister-chromatid cohesion, and suggest that the chromosomal instability may be the underlying cause of cancer predisposition and birth defects in these mutant mice.
Deficiency of Bloom syndrome helicase activity is radiomimetic
TLDR
It is shown that BLM-knockout colorectal cancer cells exhibited endogenous, ATM-dependent double-strand DNA break responses similar to those recently observed in Bloom syndrome patient-derived cells, suggesting that pharmacological inhibitors of BLM would have a radiomimetic effect, and that transient inhibition of BLM activity might be a viable strategy for anticancer therapy.
The Bloom's syndrome helicase suppresses crossing over during homologous recombination
TLDR
It is shown that mutations in BLM and hTOPO IIIα together effect the resolution of a recombination intermediate containing a double Holliday junction and prevents exchange of flanking sequences, which has wider implications for the understanding of the process of homologous recombination and the mechanisms that exist to prevent tumorigenesis.
Carcinogens induce genome-wide loss of heterozygosity in normal stem cells without persistent chromosomal instability.
TLDR
It is suggested that LOH contributes significantly to the carcinogenicity of a variety of mutagens and raises the possibility that genome-wide LOH observed in some human cancers may reflect prior exposure to genotoxic agents rather than a state of chromosomal instability during the carcinogenic process.
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  • G. Luo, M. Yao, J. Petrini
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
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