Artículos de revistas
Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks
Fecha
2016-01-14Registro en:
Federico, Maria Belén; Vallerga, María ; Radl, Daniela Betiana; Paviolo, Natalia Soledad; Bocco, Jose Luis; et al.; Chromosomal integrity after UV irradiation requires FANCD2-mediated repair of double strand breaks; Public Library of Science; Plos Genetics; 14-1-2016
1553-7390
1553-7404
CONICET Digital
CONICET
Autor
Federico, Maria Belén
Vallerga, María
Radl, Daniela Betiana
Paviolo, Natalia Soledad
Bocco, Jose Luis
Di Giorgio, Marina
Soria, Gastón
Gottifredi, Vanesa
Resumen
Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.