{"id":366,"date":"2026-09-21T08:26:34","date_gmt":"2026-09-21T08:26:34","guid":{"rendered":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/?page_id=366"},"modified":"2026-09-21T09:44:20","modified_gmt":"2026-09-21T09:44:20","slug":"spop-and-dna-repair","status":"publish","type":"page","link":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/en\/research-themes\/spop-and-dna-repair\/","title":{"rendered":"SPOP and DNA Repair"},"content":{"rendered":"\n
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Molecular Mechanisms of Prostate Cancer and DNA Repair<\/h3>\n\n\n\n

SPOP (Speckle-type POZ protein)<\/strong> is a component of a ubiquitin ligase complex that regulates protein degradation and is one of the most frequently mutated genes in prostate cancer.<\/p>\n\n\n\n

We investigate how SPOP contributes to DNA repair and the maintenance of genomic stability<\/strong> in prostate cancer cells. In particular, we have focused on the relationship between SPOP and topoisomerase II alpha (TOP2A)<\/strong> and the DNA damage associated with TOP2A activity.<\/p>\n<\/div>\n\n\n\n

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Loss of SPOP Function Leads to Accumulation of DNA Damage<\/h3>\n\n\n\n

In AR-positive prostate cancer cells, suppression of SPOP resulted in increased levels of \u03b3H2AX<\/strong>, a marker of DNA damage.<\/p>\n\n\n\n

We further demonstrated that loss of SPOP function impairs the removal of DNA-bound TOP2A, leading to the accumulation of TOP2A\u2013DNA cleavage complexes<\/strong>.<\/p>\n<\/div>\n\n\n\n

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Mechanism for Removing TOP2A from DNA<\/h3>\n\n\n\n

TOP2A is an essential enzyme that resolves topological constraints arising during DNA replication, but it transiently forms covalent complexes with DNA during this process.<\/p>\n\n\n\n

Our studies indicate that SPOP facilitates the removal of DNA-bound TOP2A through DNA repair-associated proteins, including TDP1 and TDP2<\/strong>.<\/p>\n\n\n\n

When SPOP function is impaired, TOP2A accumulates on DNA, potentially leading to DNA double-strand breaks and genomic instability<\/strong>.<\/p>\n\n\n\n

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Cancer-Associated SPOP Mutations Alter DNA Repair<\/h3>\n\n\n\n

Expression of the prostate cancer-associated SPOP F133V mutation<\/strong> resulted in nuclear accumulation of TOP2A and increased \u03b3H2AX.<\/p>\n\n\n\n

The F133V mutation was also associated with reduced expression of TDP2 and MRE11<\/strong>, suggesting that disruption of DNA repair mechanisms by SPOP mutations may contribute to genomic instability and prostate cancer progression<\/strong>.<\/p>\n<\/div>\n\n\n\n

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From Molecular Mechanisms to Novel Therapeutic Strategies<\/h3>\n\n\n\n

Abnormalities in DNA repair mechanisms are involved not only in the development and progression of prostate cancer but also in treatment response<\/strong>.<\/p>\n\n\n\n

By further elucidating the interplay among SPOP, TOP2A, AR signaling, and DNA repair<\/strong>, we aim to develop novel therapeutic strategies tailored to the molecular characteristics of prostate cancer<\/strong>.<\/p>\n<\/div>\n\n\n\n

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\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000\u3000Watanabe et al. Mol. Bio. of the Cell 2020<\/p>\n\n\n\n

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Related Publications<\/h2>\n\n\n\n

SPOP is essential for DNA-protein cross-link repair in prostate cancer cells: SPOP-dependent removal of topoisomerase 2A from the topoisomerase 2A-DNA cleavage complex<\/strong>
Watanabe R, Maekawa M, Hieda M, Taguchi T, Miura N, Kikugawa T, Saika T, Higashiyama S.
Mol Biol Cell. 2020 Mar 15;31(6):478-490.<\/em>
PMID: 31967940<\/a><\/p>\n\n\n\n

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Molecular Mechanisms of Prostate Cancer and DNA Repair SPOP (Speckle-type POZ protein) is a component of a ubi […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":376,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"sns_share_botton_hide":"","vkExUnit_sns_title":"","_vk_print_noindex":"","sitemap_hide":"","vkExUnit_sitemap":"","_veu_custom_css":"","veu_display_promotion_alert":"","_exclude_from_list_pages":"","vkexunit_cta_each_option":"","vkExUnit_childPageIndex":"","vkExUnit_pageList_ancestor":"","vkExUnit_contact_enable":"","_lightning_design_setting":{"layout":"col-one-no-subsection"},"footnotes":""},"class_list":["post-366","page","type-page","status-publish","hentry"],"veu_head_title_object":{"title":"","add_site_title":""},"_links":{"self":[{"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/366","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/comments?post=366"}],"version-history":[{"count":2,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/366\/revisions"}],"predecessor-version":[{"id":368,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/366\/revisions\/368"}],"up":[{"embeddable":true,"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/pages\/376"}],"wp:attachment":[{"href":"https:\/\/www.m.ehime-u.ac.jp\/school\/epcrc\/wp-json\/wp\/v2\/media?parent=366"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}