Patients with ataxia telangiectasia (AT) syndrome exhibit a high level of spontaneous chromosome aberrations, with hypersensitivity to gamma radiation and radiomimetic chemicals at the chromosomal and cellular level. Previously pregnancies at risk for AT have been screened solely by analysis of amniotic fluid samples. In this report we describe a cytogenetic approach to the prenatal diagnosis o...

Replication-dependent chromosomal breakage suggests that replication forks occasionally run into nicks in template DNA and collapse, generating double-strand ends. To model replication fork collapse in vivo, I constructed phage lambda chromosomes carrying the nicking site of M13 bacteriophage and infected with these substrates Escherichia coli cells, producing M13 nicking enzyme. I detected dou...

We compared the genome of the nematode Caenorhabditis elegans to 13% of that of Caenorhabditis briggsae, identifying 252 conserved segments along their chromosomes. We detected 517 chromosomal rearrangements, with the ratio of translocations to inversions to transpositions being approximately 1:1:2. We estimate that the species diverged 50-120 million years ago, and that since then there have b...

Chromosomal regions of identical or nearly identical DNA sequence can preferentially associate with one another in the apparent absence of DNA breakage. Molecular mechanism(s) underlying such homology-dependent pairing phenomena remain(s) unknown. Using Neurospora crassa repeat-induced point mutation (RIP) as a model system, we show that a pair of DNA segments can be recognized as homologous, i...

BACKGROUND Nijmegen Breakage Syndrome(NBS) is a rare autosomal recessive disorder with specific clinical features, characteristic chromosomal breakage and combined imunodeficiency. Patients with this condition also associate growth retardation with microcephaly, predisposition to malignancy and specific skin manifestations. CASE PRESENTATION Here we report a 3-year old girl known with NBS ass...

Benzene is a widely recognized human and animal carcinogen. In spite of considerable research, relatively little is known about the genotoxic events that accompany benzene exposure in vivo. To gain insights into the mechanisms underlying the genotoxic effects of benzene, we have characterized the origin of the micronuclei that are formed in bone marrow erythrocytes and splenic lymphocytes of be...

DNA sequences capable of adopting non-canonical secondary structures have been associated with gross-chromosomal rearrangements in humans and model organisms. Previously, we have shown that long inverted repeats that form hairpin and cruciform structures and triplex-forming GAA/TTC repeats induce the formation of double-strand breaks which trigger genome instability in yeast. In this study, we ...

Human chromosomal fragile sites are specific genomic regions which exhibit gaps or breaks on metaphase chromosomes following conditions of partial replication stress. Fragile sites often coincide with genes that are frequently rearranged or deleted in human cancers, with over half of cancer-specific translocations containing breakpoints within fragile sites. But until recently, little direct ev...

Chromosomal rearrangement (CR) events result from abnormal breaking and rejoining of the DNA molecules, or from crossing-over between repetitive DNA sequences, and they are involved in many tumor and non-tumor diseases. Investigations of disease-associated CR events can not only lead to important discoveries about DNA breakage and repair mechanisms, but also offer important clues about the path...

Fanconi anemia is an inherited cancer predisposition disease characterized by cytogenetic and cellular hypersensitivity to cross-linking agents. Seeking evidence of Fanconi anemia protein dysfunction in women at risk of ovarian cancer, we screened ovarian surface epithelial cells from 25 primary cultures established from 22 patients using cross-linker hypersensitivity assays. Samples were obtai...