{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe Rad9 gene family is evolutionarily conserved and plays a central role in preserving genomic integrity through multiple processes including DNA repair, cell cycle checkpoint control, and the regulation of apoptosis. In this context, the canonical Rad9 protein has been shown to participate in diverse molecular activities that maintain genome stability and modulate stress responses (‑"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "‑).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have uncovered that the human paralogue RAD9B exhibits distinct regulatory functions compared to its counterpart RAD9A. Overexpression experiments demonstrate that while RAD9A supports routine DNA damage responses, RAD9B uniquely delays cells in the G1 phase and relocates to the nucleoli following nucleolar stress. This nucleolar targeting, critically dependent on its C-terminal tail, implicates RAD9B in modulating checkpoint pathways and orchestrating a specific stress response (‑"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "‑).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, emerging genetic studies have linked rare deleterious variants of RAD9B with neural tube defects in humans. Functional analyses reveal that specific mutations – including frameshifts and missense changes – impair RAD9B’s nuclear localization, diminish protein levels, and reduce its capacity to activate the JNK signaling cascade. These deficits ultimately compromise cell proliferation and proper differentiation in early neural development, as evidenced by disrupted expression of key developmental markers and aberrant neural organoid formation, highlighting a crucial role for RAD9B in embryonic neural morphogenesis and cell adhesion regulation (‑"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "‑).\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its developmental functions, RAD9B shares important activities in the DNA damage response network. As a paralog of RAD9A, RAD9B contributes to resistance against genotoxic stress and apoptotic regulation by forming part of the 9‐1‐1 complex with RAD1 and HUS1. Such roles not only underpin cellular defense mechanisms against DNA damage but also provide insight into how dysfunction in these pathways may be associated with neurodegenerative conditions such as Parkinson’s disease (‑"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "‑).\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Howard B Lieberman "}, {"type": "b", "children": [{"type": "t", "text": "Rad9, an evolutionarily conserved gene with multiple functions for preserving genomic integrity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.20759"}], "href": "https://doi.org/10.1002/jcb.20759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16365875"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16365875"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Antonio Jesús Pérez-Castro, Raimundo Freire "}, {"type": "b", "children": [{"type": "t", "text": "Rad9B responds to nucleolar stress through ATR and JNK signalling, and delays the G1-S transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.091124"}], "href": "https://doi.org/10.1242/jcs.091124"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22399810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22399810"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xuanye Cao, Tian Tian, John W Steele, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of RAD9B impairs early neural development and contributes to the risk for human spina bifida."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.23969"}], "href": "https://doi.org/10.1002/humu.23969"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31898828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31898828"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Pedro Barroso-Chinea, Josmar Salas-Hernández, Ignacio Cruz-Muros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of RAD9B in the mesostriatal system of rats and humans: Overexpression in a 6-OHDA rat model of Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Anat (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.aanat.2023.152135"}], "href": "https://doi.org/10.1016/j.aanat.2023.152135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37460044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37460044"}]}]}]}