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Query: UNIPROT:Q9UIJ5 (
Rec
)
58,342
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations were induced in Neurospora which cause increased sensitivity to MMS (methyl methane-sulfonate) and other mutagens. Genetic analysis of such mus demonstrated that some of them defined new DNA repair genes (mus-21, and mus-27 to mus-30), while others represented new alleles in previously known genes. To characterize them further, and especially to identify
rec
- types which have not yet been found in this species, many MMS-sensitive strains were tested for cross-sensitivities to bleomycin (BLM) and to hydrogen peroxide (H2O2) to which some
rec
- of other species are hypersensitive. In Neurospora, many of the MMS-sensitive mutants were found to be cross-sensitive to BLM and frequently these were also hypersensitive to ionizing radiation.
Bleomycin
sensitivity was demonstrated for all alleles of 10 different genes, 4 of them new ones, with mus-27 being the most sensitive of the latter (resembling uvs-6; Koga and Schroeder, 1987, Mutation Res., 183, 139). In contrast, very few of the MMS-sensitive mutants were hypersensitive to H2O2 and, in general, results of H2O2 tests were variable and differences between strains small. However, consistent deviations from wild type were observed in a few cases (most clearly for mus-9 and mus-11) when results from treatments of germinating conidia were compared with those of non-growing ones.
...
PMID:Sensitivity to bleomycin and hydrogen peroxide of DNA repair-defective mutants in Neurospora crassa. 246 86
We have used intratracheal instillation of bleomycin in rats to study the microanatomical changes of blood vessels associated with lung fibrosis.
Bleomycin
is a toxic cytostatic drug employed in classical models of lung fibrosis. Wistar rats were submitted to intratracheal injection of 1.5 units of bleomycin and sacrificed 2.5 months later, a timing when marked fibrosis of the lung is observed. We casted the vascular tree of the rat lungs by perfusion with a methacrylate resin. These casts were studied by scanning electron microscopy. Lung tissue was also studied by light microscopy and thin section electron microscopy. The major vascular modifications observed in the bleomycin-treated rats were: (1) neoformation of an elaborate network of vessels located in the peribronchial domains of the lung, and (2) distortion of the architecture of alveolar capillaries. By light microscopy, it was clear that the newly formed vascular network was located in regions of fibrosis (which in the resin casts were digested away). These neoformed vessels appeared to originate from bronchial arteries. Thin section electron microscopy revealed that endothelial cells of the neoformed vessels were plump, presented large nuclei, and showed numerous pinocytotic vesicles that were also observed in subendothelial pericytes. The alveoli of the bleomycin-treated rats were heterogeneous in size and shape in contrast with the homogeneity of alveoli of control animals. The alveolar capillaries of fibrotic lungs appeared to occupy a larger volume of the alveolar wall than alveolar capillaries of control rats. Our findings indicate that lung fibrosis encompasses marked changes of the vascular system, namely, the neoformation of vessels and the rearrangement of alveolar capillaries. These structural changes suggest that fibrotic transformation of the lung is associated with the local generation of angiogenic stimuli.
Anat
Rec
1994 Jan
PMID:Neoformation of blood vessels in association with rat lung fibrosis induced by bleomycin. 750 80
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.
...
PMID:Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis. 1595 Mar 75
Telomeres are composed of specialized chromatin that includes DNA repair/recombination proteins, telomere DNA-binding proteins and a number of three dimensional nucleic acid structures including G-quartets and D-loops. A number of studies suggest that the
BLM
and WRN recQ-like helicases play important roles in recombination-mediated mechanisms of telomere elongation or Alternative Lengthening of Telomeres (ALT), processes that maintain/elongate telomeres in the absence of telomerase.
BLM
and WRN localize within ALT-associated nuclear bodies in telomerase-negative immortalized cell lines and interact with the telomere-specific proteins POT1, TRF1 and TRF2. Helicase activity is modulated by these interactions.
BLM
functions in DNA double-strand break repair processes such as non-homologous end joining, homologous recombination-mediated repair, resolution of stalled replication forks and synthesis-dependent strand annealing, although its precise functions at the telomeres are speculative. WRN also functions in DNA replication, recombination and repair, and in addition to its helicase domain, includes an exonuclease domain not found in other recQ-like helicases. The biochemical properties of
BLM
and WRN are, therefore, important in biological processes other than DNA replication, recombination and repair. In this review, we discuss some previous and recent findings of human
rec
-Q-like helicases and their role in telomere elongation during ALT processes.
...
PMID:Unwinding protein complexes in ALTernative telomere maintenance. 1991 88