Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bloom syndrome (BS) is a human cancer-prone genetic disorder essentially characterized by a generalized genetic instability including a high level of sister chromatid exchanges (SCEs). Although mutator and hyper-Rec phenotypes of BS cells present analogies with those of bacteria and yeast defective in DNA mismatch repair, we report that (CA)(n) microsatellite alterations are undetectable in BS cells. Thus, our results suggest that the origin of BS mutator phenotype is not a major defect in DNA mismatch repair, allowing us to eliminate an attractive hypothesis for the pleiotropy of BS. We previously suggested that at least some of the intra-allelic rearrangements occurring in minisatellites could result from unequal SCEs. Although SCEs are abnormally frequent in BS cells, the present study failed to show any significant variation of the mutation rates of the two hypermutable minisatellites we analyzed. Thus, our results show that, in spite of an overall genetic instability, alterations in structural motifs known to be predisposed to instability by different mechanisms are undetectable in BS cells.
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PMID:Stability of microsatellites and minisatellites in Bloom syndrome, a human syndrome of genetic instability. 863 1

Bloom syndrome (BS) displays one of the strongest known correlations between chromosomal instability and an increased risk of malignancy at an early age. The prevention of genomic instability and cancer depends on a complex network of pathways induced in response to DNA damage and stalled replication forks, including cell-cycle checkpoints, DNA repair, and apoptosis. Several studies have demonstrated that BLM is involved in the cellular response to DNA damage and stalled replication forks. BLM interacts physically and functionally with several proteins involved in the maintenance of genome integrity and BLM is redistributed and/or phosphorylated in response to several genotoxic stresses. The data concerning the relationship between BLM and these cellular pathways are summarized and the role of BLM in the rescue of arrested replication forks is discussed. Moreover, I speculate that BLM deficiency is lethal, and that BLM-deficient cells escaping apoptotic death do so by constitutively inducing a bacterial SOS-like response including the induction of alternative replication pathway(s) dependent on recombination, contributing to the mutator and hyper-Rec phenotypes characteristic of BS cells. This mechanism may be dependent on the RAD51 gene family, and involved in carcinogenesis in the general population.
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PMID:Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis. 1595 Mar 75

Generation of meiotic crossovers in many eukaryotes requires the elimination of anti-crossover activities by using the Msh4-Msh5 heterodimer to block helicases. Msh4 and Msh5 have been lost from the flies Drosophila and Glossina, but we identified a complex of minichromosome maintenance (MCM) proteins that functionally replace Msh4-Msh5. We found that REC, an ortholog of MCM8 that evolved under strong positive selection in flies, interacts with MEI-217 and MEI-218, which arose from a previously undescribed metazoan-specific MCM protein. Meiotic crossovers were reduced in Drosophila rec, mei-217, and mei-218 mutants; however, removal of the Bloom syndrome helicase (BLM) ortholog restored crossovers. Thus, MCMs were co-opted into a novel complex that replaced the meiotic pro-crossover function of Msh4-Msh5 in flies.
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PMID:Evolution of an MCM complex in flies that promotes meiotic crossovers by blocking BLM helicase. 2322 58