Brme1-KO Mouse

Brme1, also known as C19orf57/4930432K21Rik, is a gene crucial for meiotic recombination [3]. It is involved in the DNA double-strand break (DSB) repair pathway during meiosis, which is essential for generating crossovers and the formation of haploid germ cells [1]. It associates with proteins like BRCA2, MEILB2/HSF2BP, and single-stranded DNA (ssDNA) binding proteins, playing a significant role in the recruitment of recombinases RAD51 and DMC1 to DSB sites [3].

In Brme1 knockout (Brme1-/-) mice, the BRCA2-MEILB2 complex is destabilized. This leads to defects in DSB repair, homolog synapsis, and crossover formation. Persistent DSBs in these mice reactivate the somatic-like DNA-damage response, which can repair DSBs but cannot complement the crossover formation defects [2]. Also, in Brme1 KO spermatocytes, the removal of ssDNA binding proteins from DSB sites is delayed, and the loading of RAD51 and DMC1 onto resected ssDNA is impaired, indicating its importance in meiotic recombination [3].

In conclusion, Brme1 is essential for meiotic recombination through its role in the proper localization of recombinases to DSB sites. The Brme1 KO mouse models have revealed its significance in maintaining the stability of the BRCA2-MEILB2 complex and ensuring normal meiotic processes. Defects in Brme1-related functions may potentially be associated with infertility and other meiotic-related disorders [2,3].

References:

1. Gurusaran, Manickam, Zhang, Jingjing, Zhang, Kexin, Shibuya, Hiroki, Davies, Owen R. 2024. MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination. In Nature communications, 15, 6552. doi:10.1038/s41467-024-50920-x. https://pubmed.ncbi.nlm.nih.gov/39095423/

2. Zhang, Jingjing, Gurusaran, Manickam, Fujiwara, Yasuhiro, Davies, Owen R, Shibuya, Hiroki. 2020. The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells. In Nature communications, 11, 2055. doi:10.1038/s41467-020-15954-x. https://pubmed.ncbi.nlm.nih.gov/32345962/

3. Takemoto, Kazumasa, Tani, Naoki, Takada-Horisawa, Yuki, Araki, Kimi, Ishiguro, Kei-Ichiro. . Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination. In Cell reports, 31, 107686. doi:10.1016/j.celrep.2020.107686. https://pubmed.ncbi.nlm.nih.gov/32460033/