1 Ocak 2021 Dergi makalesi Açık Erişim

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

Citation Style Language JSON

{
  "DOI": "10.1016/j.cellsig.2021.110106", 
  "abstract": "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.", 
  "author": [
    {
      "family": "Gundogdu", 
      "given": " Ramazan"
    }, 
    {
      "family": "Erdogan", 
      "given": " M. Kadir"
    }, 
    {
      "family": "Ditsiou", 
      "given": " Angeliki"
    }, 
    {
      "family": "Spanswick", 
      "given": " Victoria"
    }, 
    {
      "family": "Garcia-Gomez", 
      "given": " Juan Jose"
    }, 
    {
      "family": "Hartley", 
      "given": " John A."
    }, 
    {
      "family": "Esashi", 
      "given": " Fumiko"
    }, 
    {
      "family": "Hergovich", 
      "given": " Alexander"
    }, 
    {
      "family": "Gomez", 
      "given": " Valenti"
    }
  ], 
  "container_title": "CELLULAR SIGNALLING", 
  "id": "232808", 
  "issued": {
    "date-parts": [
      [
        2021, 
        1, 
        1
      ]
    ]
  }, 
  "title": "hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors", 
  "type": "article-journal", 
  "volume": "87"
}