Coordinated protein and DNA remodeling by human HLTF on stalled replication fork

Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14073-8. doi: 10.1073/pnas.1101951108. Epub 2011 Jul 27.

Abstract

Human helicase-like transcription factor (HLTF) exhibits ubiquitin ligase activity for proliferating cell nuclear antigen (PCNA) polyubiquitylation as well as double-stranded DNA translocase activity for remodeling stalled replication fork by fork reversal, which can support damage bypass by template switching. However, a stalled replication fork is surrounded by various DNA-binding proteins which can inhibit the access of damage bypass players, and it is unknown how these proteins become displaced. Here we reveal that HLTF has an ATP hydrolysis-dependent protein remodeling activity, by which it can remove proteins bound to the replication fork. Moreover, we demonstrate that HLTF can displace a broad spectrum of proteins such as replication protein A (RPA), PCNA, and replication factor C (RFC), thereby providing the first example for a protein clearing activity at the stalled replication fork. Our findings clarify how remodeling of a stalled replication fork can occur if it is engaged in interactions with masses of proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / metabolism*
  • DNA Replication*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Models, Biological
  • Proliferating Cell Nuclear Antigen / metabolism
  • Replication Protein A / metabolism
  • Replication Protein C / metabolism
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • HLTF protein, human
  • Proliferating Cell Nuclear Antigen
  • Replication Protein A
  • Transcription Factors
  • DNA
  • Replication Protein C