Bod1l is a gene with significant roles in multiple biological processes. It is involved in chromatin-related functions, DNA replication fork protection, and is associated with pathways like the Fanconi Anemia/homologous recombination pathways [2,3]. These functions are crucial for maintaining genome stability [2,3]. Genetic models, such as gene knockout models, are valuable for studying its functions.

In gene knockout studies, Bod1l knockout reduces leukemia cells both in vitro and in vivo, and mimics the transcriptional profiles of SETD1A knockout cells. Loss of Bod1l reduces SETD1A distribution at transcriptional start sites, induces transcriptional elongation defect, and increases RNA polymerase II content at TSS without reducing H3K4me3 [1]. Additionally, Bod1l knockout confers cellular sensitivity to replication stress, leading to uncontrolled resection of damaged replication forks due to failure to stabilize RAD51 at these forks [3].

In conclusion, Bod1l is essential for mediating chromatin-SETD1A interactions and regulating SETD1A's non-canonical function in transcription. It also plays a critical role in suppressing deleterious resection of stressed replication forks, thus maintaining genome stability. Gene knockout models of Bod1l have revealed its importance in leukemia and in replication-related disease conditions, providing insights into potential therapeutic targets [1,3].

References:

1. Hoshii, Takayuki, Kikuchi, Sota, Kujirai, Tomoya, Kurumizaka, Hitoshi, Kaneda, Atsushi. . BOD1L mediates chromatin binding and non-canonical function of H3K4 methyltransferase SETD1A. In Nucleic acids research, 52, 9463-9480. doi:10.1093/nar/gkae605. https://pubmed.ncbi.nlm.nih.gov/38989615/

2. Higgs, Martin R, Stewart, Grant S. 2016. Protection or resection: BOD1L as a novel replication fork protection factor. In Nucleus (Austin, Tex.), 7, 34-40. doi:10.1080/19491034.2016.1143183. https://pubmed.ncbi.nlm.nih.gov/26889944/

3. Higgs, Martin R, Reynolds, John J, Winczura, Alicja, Niedzwiedz, Wojciech, Stewart, Grant S. 2015. BOD1L Is Required to Suppress Deleterious Resection of Stressed Replication Forks. In Molecular cell, 59, 462-77. doi:10.1016/j.molcel.2015.06.007. https://pubmed.ncbi.nlm.nih.gov/26166705/