{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent systems‐level approaches have underscored the importance of examining poorly characterized genes as novel candidates in disease mechanisms, suggesting that genes such as FIRRM may also play unsuspected roles in cellular homeostasis and pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Such methods highlight that even genes with minimal prior annotation might regulate fundamental processes when their expression is seen to correlate with well‐studied disease‐associated networks.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, animal models and genetic studies have revealed that specific mutations can disrupt essential metabolic or structural processes. For example, a spontaneous mutation in the Agps gene in mice causes cataracts and male sterility due to faulty ether lipid synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, regulation of mitotic kinases such as PLK1 at the kinetochore is critical for accurate chromosome segregation, with factors like Apolo1 ensuring that kinase activity is finely tuned during prometaphase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " These studies collectively illustrate how precision in biochemical pathways is essential for cellular viability.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the realm of DNA repair, FIRRM – previously annotated as c1orf112/FLIP – emerges as a pivotal regulator of homologous recombination. Upon DNA damage or replication stress, FIRRM is recruited to damage foci where it forms a stable complex with FIGNL1. This interaction is critical for modulating RAD51 nucleofilament dynamics by limiting RAD51 accumulation on chromatin and promoting its timely dissociation, thereby ensuring proper repair completion and replication fork progression. Loss of FIRRM function manifests as increased chromosomal instability, replication slowing, and an overall reduction in homologous recombination competency."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sipko van Dam, Rui Cordeiro, Thomas Craig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GeneFriends: an online co-expression analysis tool to identify novel gene targets for aging and complex diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genomics (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2164-13-535"}], "href": "https://doi.org/10.1186/1471-2164-13-535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23039964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23039964"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "R Liegel, B Chang, R Dubielzig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blind sterile 2 (bs2), a hypomorphic mutation in Agps, results in cataracts and male sterility in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2011.02.002"}], "href": "https://doi.org/10.1016/j.ymgme.2011.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21353609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21353609"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Leilei Xu, Mahboob Ali, Wenxiu Duan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Feedback control of PLK1 by Apolo1 ensures accurate chromosome segregation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109343"}], "href": "https://doi.org/10.1016/j.celrep.2021.109343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34260926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34260926"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jessica D Tischler, Hiroshi Tsuchida, Rosevalentine Bosire, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-024-45139-9"}], "href": "https://doi.org/10.1038/s41467-024-45139-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38286805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38286805"}]}]}]}