{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nDCLRE1B—also known as Apollo or SNM1B—is a 5′–to–3′ exonuclease that plays a crucial role in telomere maintenance. By directly interacting with shelterin components such as TRF2, Apollo is recruited to telomeric ends where it processes newly replicated DNA to generate and maintain proper 3′ overhangs. This activity prevents telomere deprotection and the ensuing DNA‐damage response, with additional regulation provided by DNA‐PK–mediated phosphorylation that controls Apollo’s access to telomeres. Disruption of these interactions, as observed in genetic models and in certain familial cancers, leads to telomere dysfunction and genomic instability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its telomeric functions, DCLRE1B is intimately involved in the repair of DNA interstrand crosslinks (ICLs) and in orchestrating the DNA‐damage response during replication stress. Its 5′ exonuclease activity is critical for processing ICLs and facilitating downstream repair events that include homologous recombination and checkpoint activation. Apollo functions in concert with components of the Fanconi anemia pathway—such as FANCD2, FANCI, and SLX4—and other repair factors to promote efficient removal of crosslinks and to stabilize stalled replication forks, thereby preventing chromosomal breakage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and additional functional studies have further refined our understanding of DCLRE1B’s distinct biochemical properties. Crystal structures reveal a unique DNA-binding groove and a dedicated 5′ phosphate binding pocket that underpin its exonuclease specificity and reduced processivity relative to related nucleases. Moreover, Apollo has been implicated in mitotic checkpoint regulation via its interaction with proteins such as Astrin, with dysregulation of its activity correlating with poor clinical outcomes in diverse cancers. These insights underscore the multifaceted role of DCLRE1B in genome stability, spanning from telomere protection to the resolution of complex DNA repair intermediates."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Megan van Overbeek, Titia de Lange "}, {"type": "b", "children": [{"type": "t", "text": "Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2006.05.022"}], "href": "https://doi.org/10.1016/j.cub.2006.05.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16730176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16730176"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christelle Lenain, Serge Bauwens, Simon Amiard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2006.05.021"}], "href": "https://doi.org/10.1016/j.cub.2006.05.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16730175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16730175"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jing Ye, Christelle Lenain, Serge Bauwens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2010.05.032"}], "href": "https://doi.org/10.1016/j.cell.2010.05.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20655466"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20655466"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Brian D Freibaum, Christopher M Counter "}, {"type": "b", "children": [{"type": "t", "text": "hSnm1B is a novel telomere-associated protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C600038200"}], "href": "https://doi.org/10.1074/jbc.C600038200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16606622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16606622"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marco Anders, Jens Mattow, Martin Digweed, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for hSNM1B/Apollo functioning in the HSP70 mediated DNA damage response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.8.11.8605"}], "href": "https://doi.org/10.4161/cc.8.11.8605"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19411856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19411856"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Brian D Freibaum, Christopher M Counter "}, {"type": "b", "children": [{"type": "t", "text": "The protein hSnm1B is stabilized when bound to the telomere-binding protein TRF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M800388200"}], "href": "https://doi.org/10.1074/jbc.M800388200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18593705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18593705"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ceylan Sonmez, Beatrice Toia, Patrik Eickhoff, et al. 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