title: Fidelity of DNA double-strand break repair in heterozygous cell lines harbouring BRCA1 missense mutations.
abstract: Germ-line mutations of the BRCA1 and BRCA2 genes, when they lead to a truncated protein, confer a high risk of breast and ovarian cancer. However, the role of BRCA1 missense mutations in cancer predisposition is unclear. Functional assays may be very helpful to more clearly define the biological effect of these mutations, and could therefore be useful in clinical practice. A recent study using a Host Cell End-Joining assay showed that a truncating mutation results in impaired fidelity of DSB repair by DNA end-joining. In the present study, we examined the fidelity of DSB repair in four lymphoblastoid cell lines with BRCA1 missense mutations. The fidelity of DNA end-joining was impaired in the four cell lines studied compared to the normal control cell line. The fidelity of end-joining was similar to that of a truncated mutation control cell line for one cell line and slightly higher for the other cell lines.
authors.affiliation: Service de Génétique Oncologique, Institut Curie 26, rue d'Ulm, Section Médicale, Paris Cedex 05 75248, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupier
authors.forename: Céline
authors.initials: C
authors.lastname: Baldeyron
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rousseau
authors.forename: Véronique
authors.initials: V
authors.lastname: Mosseri
authors.forename: Sabine
authors.initials: S
authors.lastname: Pages-Berhouet
authors.forename: Virginie
authors.initials: V
authors.lastname: Caux-Moncoutier
authors.forename: Dora
authors.initials: D
authors.lastname: Papadopoulo
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
mesh_terms: D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D019398:Genes, BRCA1; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense