All living organisms need to duplicate their genetic information while protecting it from unwanted mutations, which can lead to genetic disorders and cancer development. Inaccuracies during DNA replication are the major cause of genomic instability, as replication forks are prone to stalling and collapse, resulting in DNA damage. The presence of exogenous DNA damaging agents as well as endogeno...

Genomic stability is a commitment of regulation and establishment of cell lines in organisms. The instability of genomes greatly affects maintenance of genetic profile and is directly or indirectly associated with many disorders. With the exception of cancer, genomic instability is widely associated with neurodegenerative disorders. The conflicts among the molecular mechanisms, such as replicat...

Cancer is caused by successive gene mutations that amount to confer malignant phenotype. Genomic instability is considered a key endogenous mechanism for accumulation of mutations, and therefore, has been proposed as an engine of tumorigenesis. Recently, cancer stem cells, or tumor initiating cells, have been identified in a variety of human cancers. These cancer stem cells are believed to be r...

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by a truncated lamin A protein (progerin) that drives cellular and organismal decline. HGPS patient-derived fibroblasts accumulate genomic instability, but its underlying mechanisms and contribution to disease remain poorly understood. Here, we show that progerin-induced replication stress (RS) drives genomic instab...

Alu-PCR is a relatively simple technique that can be used to investigate genomic instability in cancer. This technique allows identification of the loss, gain or amplification of gene sequences based on the analysis of segments between two Alu elements coupled with quantitative and qualitative analyses of the profiles obtained from tumor samples, surgical margins and blood. In this work, we use...

The main results of the EC project ‘Genomic instability and radiation-induced cancer’ (RADINSTAB) are reviewed and the potential implications of genomic instability and bystander effect for risk assessment and radiation protection discussed. A basic paradigm in radiobiology is that, after exposure to ionising radiation, the deposition of energy in the cell nucleus and the resulting damage to DN...

Genomic instability is a conserved factor in lifespan reduction, although the molecular mechanism is not known. Studies in the yeast Saccharomyces cerevisiae over the past 20 years have found a connection between the ribosomal RNA gene cluster (rDNA) and lifespan. The highly repetitive rDNA exhibits genomic instability, and the antiaging histone deacetylase gene SIR2 regulates this instability....