Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use a model Saccharomyces cerevisiae system to characterize genome instability mediated by yeast telomeric (Ytel) repeats embedded within an int...

DNA damage recognition subunits such as DDB2 and XPC protect the human skin from ultraviolet (UV) light-induced genome instability and cancer, as demonstrated by the devastating inherited syndrome xeroderma pigmentosum. Here we show that the beneficial DNA repair response triggered by these two genome caretakers critically depends on a dynamic spatiotemporal regulation of their homeostasis. The...

The majority of adult human epithelial cancers exhibit evidence of genetic instability, and it is widely believed that the genetic instability manifested by aneuploidy or microsatellite instability plays an essential role in the genesis of these tumors. Indeed, most experimental models of cancer also show evidence of genomic instability. The resulting genetic chaos, which has widespread effects...

Due to genome instability, most cancers exhibit loss of regions containing tumor suppressor genes and collateral loss of other genes. To identify cancer-specific vulnerabilities that are the result of copy number losses, we performed integrated analyses of genome-wide copy number and RNAi profiles and identified 56 genes for which gene suppression specifically inhibited the proliferation of cel...

The genome of Pelosinus fermentans JBW45, isolated from a chromium-contaminated site in Hanford, Washington, USA, has been completed with PacBio sequencing. Nine copies of the rRNA gene operon and multiple transposase genes with identical sequences resulted in breaks in the original draft genome and may suggest genomic instability of JBW45.

The yeast sirtuin (Sir2) is a histone deacetylase that modulates yeast replicative life span by suppressing genome instability through chromatin modification. In this issue, Oberdoerffer et al. (2008) report that SIRT1, the mammalian ortholog of Sir2, is involved in DNA damage-induced chromatin reorganization, which promotes genome stability in mammalian cells.

A putative translocation line (#32), together with a disomic addition line (TAI27) and an octo-amphiploid line (Zhong3) of common wheat and Thinopyrum intermedium were characterized by restriction fragment length polymorphism (RFLP) analysis, using probes covering all seven homoeologous groups of Triticeae. Line 32 was confirmed to be a cryptic translocation line, based on the detection of mult...

Mitochondrial DNA has been proposed to be involved in carcinogenesis because of high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. In this paper, we review mitochondrial genome instability, relation of mitochondrial DNA mutations with apoptosis and mitochondrial genomic aberrations reported in solid tumors of the thyroid, colorectal, breast, and gastric

Two forms of genetic instability have been described in colorectal cancer: chromosomal instability, characterized by structural and numerical chromosomal abnormalities and associated to aneuploidy; and microsatellite instability, characterized by a deficiency in the mismatch repair system that leads to slippage in microsatellites and is associated to euploidy. Thirteen colorectal cancer sample ...

Genome instability is linked to cancer and many hereditary diseases. Chromosomal aberrations are often associated with repeats that can adopt DNA secondary structures. Studying the mechanism of genome instability caused by unstable motifs will therefore contribute to our understanding of the origin of human pathology. In this study, we investigate the mechanism underlying inverted repeated asso...