Understanding DNA replication and replication stress as avenues to combat cancer.

The Collection “DNA Replication and Replication Stress” brings together original research articles, critical reviews, and perspectives from scientists with diverse viewpoints and areas of expertise in DNA replication, genome integrity, and cancer.

FANCD2 promotes mitotic rescue from transcription-mediated replication stress in SETX-deficient cancer cells.

Replication stress (RS) is a leading cause of genome instability and cancer development. A substantial source of endogenous RS originates from the encounter between the transcription and replication machineries operating on the same DNA template. This occurs predominantly under specific contexts, such as oncogene activation, metabolic stress, or a deficiency in proteins that specifically act to prevent or resolve those transcription-replication conflicts (TRCs).

FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability.

Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells.

The passage from bone marrow niche to bloodstream triggers the metabolic impairment in Fanconi Anemia mononuclear cells.

Fanconi Anemia (FA) is a disease characterized by bone marrow (BM) failure and aplastic anemia. In addition to a defective DNA repair system, other mechanisms are involved in its pathogenesis, such as defective mitochondrial metabolism, accumulation of lipids, and increment of oxidative stress production. To better understand the role of these metabolic alterations in the process of HSC maturation in FA, we evaluated several biochemical and cellular parameters on mononuclear cells isolated from the bone marrow of FA patients or healthy donors.