{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNASEH2B is a non‐catalytic subunit of the ribonuclease H2 complex that is essential for maintaining genome stability. In human cells, RNASEH2B not only helps assemble the trimeric complex with RNASEH2A—the catalytic subunit—and RNASEH2C, but it also facilitates the complex’s timely import into the nucleus and its recruitment to sites of DNA replication and repair. Importantly, RNASEH2B contains a PCNA‐interacting (PIP) motif that mediates binding to the replication machinery, while interactions with other factors such as chromatin modulators further enable the efficient processing of mis‐incorporated ribonucleotides and resolution of RNA/DNA hybrids. These functions are crucial for coordinating ribonucleotide excision repair and non‐homologous end joining, thereby protecting the genome from DNA damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in RNASEH2B are among the genetic alterations that cause Aicardi‐Goutières syndrome (AGS), an inflammatory encephalopathy marked by elevated type I interferon responses. In this context, a failure to properly excise mis‐incorporated ribonucleotides leads to the accumulation of nucleic acid species that in turn trigger innate immune activation. Notably, patients with RNASEH2B mutations often display a later-onset clinical presentation relative to other AGS genotypes, highlighting a genotype–phenotype correlation where RNASEH2B dysfunction perturbs normal nucleotide metabolism and interferon homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have also implicated RNASEH2B in cancer biology. Deleterious variants or loss of RNASEH2B contribute to genomic instability that can alter therapeutic responses. For example, in prostate cancer, deletion of RNASEH2B is associated with heightened sensitivity to poly(ADP‐ribose) polymerase (PARP) inhibitors, although the effect can be modulated by concurrent alterations in genes such as RB1 and BRCA2. Similarly, emerging evidence from ovarian cancer and leukemic T‐cell models underscores that RNASEH2B deficits can compromise cell cycle progression and DNA repair, thereby shaping both disease progression and treatment outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hyongi Chon, Alex Vassilev, Melvin L DePamphilis, et al. 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