{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEM1 (also known as DSS1) is a small, highly acidic, intrinsically disordered protein that plays a pivotal role in genome maintenance by directly modulating homologous recombination repair. It associates with the BRCA2 protein and influences the handoff of single‐stranded DNA to RAD51, thereby promoting accurate double‐strand break repair. SEM1 executes these functions by serving as a molecular adaptor that regulates BRCA2 oligomerization, restrains inappropriate double‐stranded DNA binding, and even acts as a DNA mimic to attenuate the affinity of replication protein A (RPA) for single‐stranded DNA. In addition, SEM1 enhances the activities of other repair proteins such as RAD52 by modulating their oligomeric states and DNA binding properties, thereby promoting efficient single‐strand annealing and break-induced replication."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its central role in DNA repair, SEM1 is an integral component of the 26S proteasome complex. Here it contributes to proteasome assembly and function by interacting directly with regulatory subunits such as RPN3 and RPN7. This association is critical not only for the recruitment of polyubiquitinated substrates (including key tumor suppressors like p53) for targeted degradation but also for the regulation of mRNA export and RNA processing via its participation in multisubunit complexes (for example, those involved in splicing, transcription regulation, and mRNA nuclear export). Its versatility as a polyanionic adhesive allows SEM1 to stabilize protein assemblies by preventing nonproductive interactions, thereby supporting diverse cellular functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant expression or mutation of SEM1 has significant clinical and oncogenic implications. In many cancer types—including breast, cervical, and glioma—altered SEM1 levels have been linked to defective homologous recombination repair, genomic instability, and chemoresistance. Notably, reduced or dysfunctional SEM1 impairs BRCA2-dependent repair processes, while overexpression has been associated with tumor progression and poor clinical outcomes. Moreover, SEM1’s regulation of proteasomal activity can influence the balance between error‐free and error‐prone double-strand break repair pathways, further impacting cancer development and therapeutic responses. Comparative structural analyses suggest that slight variations in SEM1’s disordered regions may underlie its divergent binding properties and functional outcomes, emphasizing its critical role in cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Colleen N Kristensen, Karin M Bystol, Boran Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkz1052"}], "href": "https://doi.org/10.1093/nar/gkz1052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31799622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31799622"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hang Phuong Le, Xiaoyan Ma, Jorge Vaquero, et al. 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