Telomere instability results from chromosome end loss (due to chromosome breakage at one or both ends) or, more frequently, telomere dysfunction. Dysfunctional telomeres arise when they lose their end-capping function or become critically short, which causes chromosomal termini to behave like a DNA double-strand break. At the chromosomal level, this phenomenon is visualized by using Fluorescenc...

Meiotic recombination is initiated by DNA double-strand breaks (DSBs) made by Spo11 (Rec12 in fission yeast), which becomes covalently linked to the DSB ends. Like recombination events, DSBs occur at hotspots in the genome, but the genetic factors responsible for most hotspots have remained elusive. Here we describe in fission yeast the genome-wide distribution of meiosis-specific Rec12-DNA lin...

A broad spectrum of mutations in PTEN, encoding a lipid phosphatase that inactivates the P13-K/AKT pathway, is found associated with primary tumors. Some of these mutations occur outside the phosphatase domain, suggesting that additional activities of PTEN function in tumor suppression. We report a nuclear function for PTEN in controlling chromosomal integrity. Disruption of Pten leads to exten...

OR some time it has been generally considered that the production of F chromosomal aberrations in Tradescantia and many other materials is essentially independent of the wave length of the exciting radiation in the region shorter than 1.5 A. This view has not been seriously questioned in recent years and to date has remained one of the fundamental tenets of radiobiology. A number of isolated in...

Cyclophosphamide, an extensively used cancer chemotherapeutic agent, requires metabolic activation through a mixed-function oxygenase system. The capacity of this agent to produce oncogenic transformation and chromosomal damage, including increases in sister chromatid exchanges, was investigated in cell culture with or without an exogenous liver metabolic activation system. No oncogenic transfo...

Composite or closely linked maize (Zea mays) Ac/Ds transposable elements can induce chromosome breakage, but the precise configurations of Ac/Ds elements that can lead to chromosome breakage are not completely defined. Here, we determined the structures and chromosome breakage properties of 15 maize p1 alleles: each allele contains a fixed fractured Ac (fAc) element and a closely linked full-le...

BACKGROUND Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability disorder with hypersensitivity to ionising radiation. The clinical phenotype is characterised by congenital microcephaly, mild dysmorphic facial appearance, growth retardation, immunodeficiency, and greatly increased risk for lymphoreticular malignancy. Most NBS patients are of Slavic origin and homozy...

In situ hybridization with whole chromosome painting probes (chromosome 1, 7, 11, 14, 17 and 21) in combination with a human pancentromeric alpha-satellite probe was used to analyse the presence of specific chromosomal material in micronuclei (MN) induced in human lymphocytes by ionizing radiation. The purpose was to investigate the nature of radiation-induced cytogenetic damage, especially to ...

Genomic instability is thought to underlie tumor progression in solid tumors, such as breast cancer. Although evidence that the hereditary breast cancer genes, BRCA1 and BRCA2, are involved in DNA repair suggests that genomic instability plays an important role in hereditary breast tumorigenesis, genomic instability remains poorly characterized in sporadic breast cancers. Using a DNA fingerprin...

Using human lymphocytes from a group of 20 donors, we investigated (i) the X-ray-induced adaptive response (AR) after four different conditioning treatments of 1, 2, 4 and 6 cGy, (ii) chromosomal sensitivity to X-irradiation during G(2) and (iii) the G(2)/M checkpoint response. An AR was found in 11 of the 18 donors (approximately 60%). No correlation was found between the presence of AR and G(...