Macromolecular crowding induces compaction and DNA binding in the disordered N-terminal domain of hUNG2

Gaddiel Rodriguez, Benjamin Orris, Ananya Majumdar, Shridhar Bhat, James T. Stivers

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Many human DNA repair proteins have disordered domains at their N- or C-termini with poorly defined biological functions. We recently reported that the partially structured N-terminal domain (NTD) of human uracil DNA glycosylase 2 (hUNG2), functions to enhance DNA translocation in crowded environments and also targets the enzyme to single-stranded/double-stranded DNA junctions. To understand the structural basis for these effects we now report high-resolution heteronuclear NMR studies of the isolated NTD in the presence and absence of an inert macromolecular crowding agent (PEG8K). Compared to dilute buffer, we find that crowding reduces the degrees of freedom for the structural ensemble, increases the order of a PCNA binding motif and dramatically promotes binding of the NTD for DNA through a conformational selection mechanism. These findings shed new light on the function of this disordered domain in the context of the crowded nuclear environment.

Original languageEnglish (US)
Article number102764
JournalDNA Repair
StatePublished - Feb 2020


  • Conformational selection
  • DNA binding
  • Intrinsically disordered protein
  • Molecular crowding
  • N-terminal domain
  • NMR spectroscopy
  • hUNG2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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