Phosphorylation of xeroderma pigmentosum group C regulates ultraviolet-induced DNA damage repair

Nucleic Acids Res. 2018 Jun 1;46(10):5050-5060. doi: 10.1093/nar/gky239.

Abstract

Nucleotide excision repair (NER) is the most versatile DNA repair system that removes bulky DNA damage induced by various endogenous and exogenous factors, including UV radiation. Defects in NER can lead to the xeroderma pigmentosum (XP) syndrome, mainly characterized by increased carcinogenesis in the skin. The function of NER factors, including xeroderma pigmentosum group C (XPC), can be regulated by post-translational modifications such as ubiquitination. However, the role of phosphorylation in XPC function remains unknown. Here, we show that phosphorylation of XPC acts as a novel post-translational regulatory mechanism of the NER pathway. We show that XPC is phosphorylated at serine 94. Moreover, after UVB irradiation, XPC phosphorylation regulates recruitment of ubiquitinated XPC and its downstream NER factors to the chromatin. In addition, upon evaluating the predicted kinases for XPC phosphorylation, we found that casein kinase II (CK2) promotes NER. Furthermore, CK2 kinase mediates XPC phosphorylation at serine 94, and also promotes recruitment of ubiquitinated XPC to the chromatin after UVB irradiation. Our findings have identified XPC phosphorylation as a new mechanism for regulating NER following UV-induced DNA damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism
  • Cell Line
  • Cell Proliferation / radiation effects
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA Damage / radiation effects
  • DNA Repair / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Keratinocytes / radiation effects
  • Phosphorylation
  • Serine / metabolism
  • Ubiquitination
  • Ultraviolet Rays

Substances

  • Chromatin
  • DNA-Binding Proteins
  • XPC protein, human
  • Serine
  • Casein Kinase II