RESUMO
Meiotic crossovers are required for accurate chromosome segregation and producing new allelic combinations. Meiotic crossover numbers are tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. Here, we reveal the tumor suppressor FANCM as a meiotic anti-crossover factor in mammals. We use unique large-scale crossover analyses with both single-gamete sequencing and pedigree-based bulk-sequencing datasets to identify a genome-wide increase in crossover frequencies in Fancm-deficient mice. Gametogenesis is heavily perturbed in Fancm loss-of-function mice, which is consistent with the reproductive defects reported in humans with biallelic FANCM mutations. A portion of the gametogenesis defects can be attributed to the cGAS-STING pathway after birth. Despite the gametogenesis phenotypes in Fancm mutants, both sexes are capable of producing offspring. We propose that the anti-crossover function and role in gametogenesis of Fancm are separable and will inform diagnostic pathways for human genomic instability disorders.
RESUMO
Gravitational-wave memory manifests as a permanent distortion of an idealized gravitational-wave detector and arises generically from energetic astrophysical events. For example, binary black hole mergers are expected to emit memory bursts a little more than an order of magnitude smaller in strain than the oscillatory parent waves. We introduce the concept of "orphan memory": gravitational-wave memory for which there is no detectable parent signal. In particular, high-frequency gravitational-wave bursts (â³kHz) produce orphan memory in the LIGO/Virgo band. We show that Advanced LIGO measurements can place stringent limits on the existence of high-frequency gravitational waves, effectively increasing the LIGO bandwidth by orders of magnitude. We investigate the prospects for and implications of future searches for orphan memory.
