APLF is a novel protein of unknown function that accumulates at sites of chromosomal DNA strand breakage via forkhead-associated (FHA) domain-mediated interactions with XRCC1 and XRCC4. APLF can also accumulate at sites of chromosomal DNA strand breaks independently of the FHA domain via an unidentified mechanism that requires a highly conserved C-terminal tandem zinc finger domain. Here, we sh...

Genotoxic carcinogens which interact with DNA may produce double-strand breaks as normal intermediates of homologous mitotic recombination, and may give rise to structural chromosome aberrations and inter-chromosomal deletion-recombination. The genotoxic profile of two inhibitors of DNA topoisomerases were evaluated using an in vivo somatic w/w+ eye assay of Drosophila melanogaster for the dete...

Recently, we demonstrated chromosome instability (CIN) in human cleavage stage embryogenesis following in vitro fertilization (IVF). CIN not necessarily undermines normal human development (i.e. when remaining normal diploid blastomeres develop the embryo proper), however it can spark a spectrum of conditions, including loss of conception, genetic disease and genetic variation development. To s...

We previously showed that plasmids containing both a mammalian replication initiation region and a matrix attachment region were efficiently amplified in human cancer cells and that they were either integrated into preexisting extrachromosomal double minutes (DMs) or induced the generation of a chromosomal homogeneously staining region (HSR). In this article, we elucidated the mechanism by whic...

Chromosomal translocations in lymphoid tumors frequently result from recombination between a normally rearranging antigen receptor gene and a normally non-rearranging second locus. The possibility that the lymphocyte recombinase apparatus plays a role in determining the position of breakage at the second locus has been a matter of controversy because of the inconsistent presence of heptamer-lik...

Recurrent reciprocal translocations are present in many hematologic and mesenchymal malignancies. Because significant sequence homology is absent from translocation breakpoint junctions, non-homologous end-joining (NHEJ) pathways of DNA repair are presumed to catalyze their formation. We developed translocation reporters for use in mammalian cells from which NHEJ events can be selected after pr...

In the alternative pathway of telomere lengthening (ALT), neoplastic cell growth is prolonged by telomere recombination. We show that ALT is unexpectedly characterized by high rates of ongoing pericentromeric chromosomal instability. Combined with telomeric recombination, ALT pericentromeric instability generates neoacrocentric chromosomes. In the present studies, we describe a subgroup of ALT ...

The LINE-1, or L1, family of interspersed repeated DNA constitutes roughly 10% of the mammalian genome. Its abundance is due to duplicative transposition via an RNA intermediate, L1-encoded proteins, and reverse transcription. Although, in principle, transposition may occur in any cell type, expression and transposition of a full-length functional element in the germ line are necessary to expla...