Architecture of the human XPC DNA repair and stem cell coactivator complex

Elisa T. Zhang, Yuan He, Patricia Grob, Yick W. Fong, Eva Nogales, Robert Tjian*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The Xeroderma pigmentosum complementation group C (XPC) complex is a versatile factor involved in both nucleotide excision repair and transcriptional coactivation as a critical component of the NANOG, OCT4, and SOX2 pluripotency gene regulatory network. Here we present the structure of the human holo-XPC complex determined by single-particle electron microscopy to reveal a flexible, ear-shaped structure that undergoes localized loss of order upon DNA binding.We also determined the structure of the complete yeast homolog Rad4 holo-complex to find a similar overall architecture to the human complex, consistent with their shared DNA repair functions. Localized differences between these structures reflect an intriguing phylogenetic divergence in transcriptional capabilities that we present here. Having positioned the constituent subunits by tagging and deletion, we propose a model of key interaction interfaces that reveals the structural basis for this difference in functional conservation. Together, our findings establish a framework for understanding the structure-function relationships of the XPC complex in the interplay between transcription and DNA repair.

Original languageEnglish (US)
Pages (from-to)14817-14822
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number48
DOIs
StatePublished - Dec 1 2015

Keywords

  • Biochemistry
  • DNA repair
  • Stem cells
  • Structure
  • Transcription

ASJC Scopus subject areas

  • General

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