Centrobin plays a role in the cellular response to DNA damage

Cell Cycle. 2019 Oct;18(20):2660-2671. doi: 10.1080/15384101.2019.1654796. Epub 2019 Aug 15.

Abstract

DNA repair proteins have been found to localize to the centrosomes and defects in these proteins cause centrosome abnormality. Centrobin is a centriole-associated protein that is required for centriole duplication and microtubule stability. A recent study revealed that centrobin is a candidate substrate for ATM/ATR kinases. However, whether centrobin is involved in DNA damage response (DDR) remains unexplored. Here we show that centrobin is phosphorylated after UV exposure and that the phosphorylation is detected exclusively in the detergent/DNase I-resistant nuclear matrix. UV-induced phosphorylation of centrobin is largely dependent on ATR activity. Centrobin-depleted cells show impaired DNA damage-induced microtubule stabilization and increased sensitivity to UV radiation. Interestingly, depletion of centrobin leads to defective homologous recombination (HR) repair, which is reversed by expression of wild-type centrobin. Taken together, these results strongly suggest that centrobin plays an important role in DDR.

Keywords: ATR-dependent phosphorylation; Centrobin; DNA damage response; homologous recombination; microtubule stability.

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / antagonists & inhibitors
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Caffeine / pharmacology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • Centrioles / metabolism
  • DNA Damage / genetics*
  • DNA Damage / radiation effects*
  • DNA Repair / genetics*
  • DNA Repair / radiation effects*
  • HeLa Cells
  • Humans
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Microtubules / radiation effects
  • Nocodazole / pharmacology
  • Phosphoprotein Phosphatases / pharmacology
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Phosphorylation / radiation effects
  • Transfection
  • Ultraviolet Rays*

Substances

  • CNTROB protein, human
  • Cell Cycle Proteins
  • Caffeine
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Phosphoprotein Phosphatases
  • Nocodazole

Grants and funding

This work was supported by the Ministry of Education [2017R1D1A1A09]; Ministry of Science (KR) [2011-0030132].