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hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors

Gundogdu, Ramazan; Erdogan, M. Kadir; Ditsiou, Angeliki; Spanswick, Victoria; Garcia-Gomez, Juan Jose; Hartley, John A.; Esashi, Fumiko; Hergovich, Alexander; Gomez, Valenti


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  <dc:creator>Gundogdu, Ramazan</dc:creator>
  <dc:creator>Erdogan, M. Kadir</dc:creator>
  <dc:creator>Ditsiou, Angeliki</dc:creator>
  <dc:creator>Spanswick, Victoria</dc:creator>
  <dc:creator>Garcia-Gomez, Juan Jose</dc:creator>
  <dc:creator>Hartley, John A.</dc:creator>
  <dc:creator>Esashi, Fumiko</dc:creator>
  <dc:creator>Hergovich, Alexander</dc:creator>
  <dc:creator>Gomez, Valenti</dc:creator>
  <dc:date>2021-01-01</dc:date>
  <dc:description>Monopolar spindle-one binder (MOBs) proteins are evolutionarily conserved and contribute to various cellular signalling pathways. Recently, we reported that hMOB2 functions in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest in untransformed cells. However, the question of how hMOB2 protects cells from endogenous DNA damage accumulation remained enigmatic. Here, we uncover hMOB2 as a regulator of double-strand break (DSB) repair by homologous recombination (HR). hMOB2 supports the phosphorylation and accumulation of the RAD51 recombinase on resected single-strand DNA (ssDNA) overhangs. Physiologically, hMOB2 expression supports cancer cell survival in response to DSBinducing anti-cancer compounds. Specifically, loss of hMOB2 renders ovarian and other cancer cells more vulnerable to FDA-approved PARP inhibitors. Reduced MOB2 expression correlates with increased overall survival in patients suffering from ovarian carcinoma. Taken together, our findings suggest that hMOB2 expression may serve as a candidate stratification biomarker of patients for HR-deficiency targeted cancer therapies, such as PARP inhibitor treatments.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/232808</dc:identifier>
  <dc:identifier>oai:aperta.ulakbim.gov.tr:232808</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>CELLULAR SIGNALLING 87</dc:source>
  <dc:title>hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
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