Fancm has dual roles in the limiting of meiotic crossovers and germ cell maintenance in mammals

• DOI: 10.1016/j.xgen.2023.100349
• Publication Date: 2023-06-29T14:34:50Z
• Authors: Vanessa Tsui; Ruqian Lyu; Stevan Novakovic; Jessica M. Stringer; Jessica E.M. Dunl...; Elissah Granger; Tim Semple; Anna Leichter; Luciano G. Martel...; D. Jo Merriner; Ruijie Liu; Lucy McNeill; Nadeen Zerafa; Eva R. Hoffmann; Moira K. O’Bryan; Karla Hutt; Andrew J. Deans; Jörg Heierhorst; Davis J. McCarthy; Wayne Crismani
• Keywords: Gamete

Meiotic crossovers are required for accurate chromosome segregation and producing new allelic combinations. crossover numbers tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. Here, we reveal the tumor suppressor FANCM as meiotic anti-crossover factor in mammals. We use unique large-scale analyses with both single-gamete sequencing pedigree-based bulk-sequencing datasets to identify genome-wide increase frequencies Fancm-deficient mice. Gametogenesis is heavily perturbed Fancm loss-of-function mice, which consistent reproductive defects reported humans biallelic mutations. A portion gametogenesis can be attributed cGAS-STING pathway after birth. Despite phenotypes mutants, sexes capable offspring. propose that function role separable will inform diagnostic pathways human genomic instability disorders.