title: The FANC pathway is activated by adenovirus infection and promotes viral replication-dependent recombination.
abstract: Deciphering the crosstalk between a host cell and a virus during infection is important not only to better define viral biology but also to improve our understanding of cellular processes. We identified the FANC pathway as a helper of viral replication and recombination by searching for cellular targets that are modified by adenovirus (Ad) infection and are involved in its outcome. This pathway, which is involved in the DNA damage response and checkpoint control, is altered in Fanconi anaemia, a rare cancer predisposition syndrome. We show here that Ad5 infection activates the FANC pathway independent of the classical DNA damage response. Infection with a non-replicating Ad shows that the presence of viral DNA is not sufficient to induce the monoubiquitination of FANCD2 but still activates the DNA damage response coordinated by phospho-NBS1 and phospho-CHK1. E1A expression alone fails to induce FANCD2 monoubiquitination, indicating that a productive viral infection and/or replication is required for FANC pathway activation. Our data indicate that Ad5 infection induces FANCD2 activation to promote its own replication. Specifically, we show that FANCD2 is involved in the recombination process that accompanies viral DNA replication. This study provides evidence of a DNA damage-independent function of the FANC pathway and identifies a cellular system involved in Ad5 recombination.
authors.affiliation: University Paris-Sud, UMR8200 CNRS, Institute Gustave Roussy, Villejuif, France.
authors.forename: Gioia
authors.initials: G
authors.lastname: Cherubini
authors.forename: Valeria
authors.initials: V
authors.lastname: Naim
authors.forename: Paola
authors.initials: P
authors.lastname: Caruso
authors.forename: Romina
authors.initials: R
authors.lastname: Burla
authors.forename: Massimo
authors.initials: M
authors.lastname: Bogliolo
authors.forename: Enrico
authors.initials: E
authors.lastname: Cundari
authors.forename: Karim
authors.initials: K
authors.lastname: Benihoud
authors.forename: Isabella
authors.initials: I
authors.lastname: Saggio
authors.forename: Filippo
authors.initials: F
authors.lastname: Rosselli
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004249:DNA Damage; D004261:DNA Replication; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011995:Recombination, Genetic; D054875:Ubiquitination; D014779:Virus Replication
chemical_list: D017500:Adenovirus E1A Proteins; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins