Clear Search sequence regions


  • ATM (1)
  • cell cycle (1)
  • cell growth (1)
  • cells (8)
  • cellular (1)
  • chromatin (1)
  • clones (1)
  • dna (3)
  • dna damage (7)
  • dna repair (2)
  • factors (2)
  • humans (1)
  • NONO (16)
  • nuclear matrix (2)
  • phase (3)
  • protein human (1)
  • Rad3 (1)
  • RAD9 (1)
  • regulates phase (1)
  • risk factor (1)
  • rna (2)
  • skin cancer (1)
  • tumour (1)
  • ultraviolet rays (1)
  • Sizes of these terms reflect their relevance to your search.

    The main risk factor for skin cancer is ultraviolet (UV) exposure, which causes DNA damage. Cells respond to UV-induced DNA damage by activating the intra-S-phase checkpoint, which prevents replication fork collapse, late origin firing and stabilizes fragile sites. Recently, the 54-kDa multifunctional protein NONO was found to be involved in the non-homologous end-joining DNA repair process and in poly ADP-ribose polymerase 1 activation. Interestingly, NONO is mutated in several tumour types and emerged as a crucial factor underlying both melanoma development and progression. Therefore, we set out to evaluate whether NONO could be involved in the DNA-damage response to UV radiations. We generated NONO-silenced HeLa cell clones and found that lack of NONO decreased cell growth rate. Then, we challenged NONO-silenced cells with exposure to UV radiations and found that NONO-silenced cells, compared with control cells, continued to synthesize DNA, failed to block new origin firing and impaired CHK1S345 phosphorylation showing a defective checkpoint activation. Consistently, NONO is present at the sites of UV-induced DNA damage where it localizes to RAD9 foci. To position NONO in the DNA-damage response cascade, we analysed the loading onto chromatin of various intra-S-phase checkpoint mediators and found that NONO favours the loading of topoisomerase II-binding protein 1 acting upstream of the ATM and Rad3-related kinase activity. Strikingly, re-expression of NONO, through an sh-resistant mRNA, rescued CHK1S345 phosphorylation in NONO-silenced cells. Interestingly, NONO silencing affected cell response to UV radiations also in a melanoma cell line. Overall, our data uncover a new role for NONO in mediating the cellular response to UV-induced DNA damage.

    Citation

    L Alfano, C Costa, A Caporaso, A Altieri, P Indovina, M Macaluso, A Giordano, F Pentimalli. NONO regulates the intra-S-phase checkpoint in response to UV radiation. Oncogene. 2016 Feb 4;35(5):567-76

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 25893301

    View Full Text