title: Robust homology-directed repair within mouse mammary tissue is not specifically affected by Brca2 mutation.
abstract: The mammary gland undergoes significant proliferative stages after birth, but little is known about how the developmental changes impact DNA double-strand break (DSB) repair. Mutations in multiple genes involved in homology-directed repair (HDR), considered a particularly accurate pathway for repairing DSBs, are linked to breast cancer susceptibility, including BRCA2. Using reporter mice that express an inducible endonuclease, we find that HDR is particularly robust in mammary tissue during puberty and pregnancy, accounting for 34-40% of detected repair events, more than in other tissues examined. Brca2 hypomorphic mutation leads to HDR defects in mammary epithelium during puberty and pregnancy, including in different epithelial lineages. Notably, a similar dependence on Brca2 is observed in other proliferative tissues, including small intestine epithelium. Our results suggest that the greater reliance on HDR in the proliferating mammary gland, rather than a specific dependence on BRCA2, may increase its susceptibility to tumorigenesis incurred by BRCA2 mutation.
authors: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors: Elizabeth M
authors: EM
authors: Kass
authors: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors: Pei Xin
authors: 0000-0001-5742-3539
authors: PX
authors: Lim
authors: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors: Hildur R
authors: HR
authors: Helgadottir
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors: Mary Ellen
authors: ME
authors: Moynahan
authors: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors: Maria
authors: M
authors: Jasin
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D011247:Pregnancy; D059767:Recombinational DNA Repair; D012741:Sexual Maturation / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; C106711:BRCA2 protein, mouse