Genome instability is a hallmark of cancer. Common fragile sites (CFSs) are specific regions in the human genome that are sensitive to replication stress and are prone to genomic instability in different cancer types. Here we molecularly cloned a new CFS, FRA11H, in 11q13. The genomic region of FRA11H harbors a hotspot of chromosomal breakpoints found in different types of cancer, indicating th...

Co-transcriptional RNA-DNA hybrids (R loops) cause genome instability. To prevent harmful R loop accumulation, cells have evolved specific eukaryotic factors, one being the BRCA2 double-strand break repair protein. As BRCA2 also protects stalled replication forks and is the FANCD1 member of the Fanconi Anemia (FA) pathway, we investigated the FA role in R loop-dependent genome instability. Usin...

Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high le...

Trinucleotide repeat instability underlies >20 human hereditary disorders. These diseases include many neurological and neurodegenerative situations, such as those caused by pathogenic polyglutamine (polyQ) domains encoded by expanded CAG repeats. Although mechanisms of instability have been intensely studied, our knowledge remains limited in part due to the lack of unbiased genome-wide screens...

Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we r...

objective: the itpa gene is responsible to remove free deaminated purine nucleotides of itp, ditp and xtp from nucleotide pool of the cells. it seems that dysfunction in its activity, not only can increas the base substitution mutations frequency but also can works as a contrived factor to creating instability in genetic materials of the cells. there are several reports about the existence of s...

Genome maintenance mechanisms actively suppress genetic instability associated with cancer and aging. Some viruses provoke genetic instability by subverting the host's control of genome maintenance. Viruses have their own specialized strategies for genome maintenance, which can mimic and modify host cell processes. Here, we review some of the common features of genome maintenance utilized by vi...