Fig. 1. Physiology of Brca2^L2431P homozygous and hemizygous mice.

a Schematic representation of BRCA2 protein showing different functional domains: N-terminal PALB2 binding domain, eight BRC repeats in the middle and a C-terminal DNA binding domain consisting of a helical domain (HD) and three oligo-binding (OB) domains. BRCA2 L2520P/L2431P variant is in the HD and disrupts interaction with DSS1. b Representative images of mice of indicated genotypes at weaning (21 days). c Body weights of mice at weaning showing significantly reduced body weight of LP/KO mice compared to WT mice (n = 10, two-tailed Student’s t test, error bar- SD of mean). d Body weights of mice of indicated genotypes measured for 8 weeks post-weaning, LP/KO mice weighed less compared to the WT littermates (n = 10, one-tailed t-test: two-sample assuming unequal variances, error bar- SE of mean). e Kaplan–Meier survival curve for 800 days of mice of indicated genotypes. LP/KO mice have reduced median survival (p = 0.009, Log-rank Mantel-Cox test) compared to LP/ + and LP/LP. f Kaplan–Meier survival curve of mice of different genotypes after 8 Gy of γ-radiation, LP/KO mice showed median survival of 15 days and are extremely sensitive to radiation as compared to all other genotypes (p = 0.0001, Log-rank Mantel–Cox test).