The HARP-like domain-containing protein AH2/ZRANB3 binds to PCNA and participates in cellular response to replication stress

Mol Cell. 2012 Aug 10;47(3):410-21. doi: 10.1016/j.molcel.2012.05.025. Epub 2012 Jun 14.


Proteins with annealing activity are newly identified ATP-dependent motors that can rewind RPA-coated complementary single-stranded DNA bubbles. AH2 (annealing helicase 2, also named as ZRANB3) is the second protein with annealing activity, the function of which is still unknown. Here, we report that AH2 is recruited to stalled replication forks and that cells depleted of AH2 are hypersensitive to replication stresses. Furthermore, AH2 binds to PCNA, which is crucial for its function at stalled replication forks. Interestingly, we identified a HARP-like (HPL) domain in AH2 that is indispensible for its annealing activity in vitro and its function in vivo. Moreover, searching of HPL domain in SNF2 family of proteins led to the identification of SMARCA1 and RAD54L, both of which possess annealing activity. Thus, this study not only demonstrates the in vivo functions of AH2, but also reveals a common feature of this new subfamily of proteins with annealing activity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / physiology
  • Conserved Sequence / physiology
  • DNA Damage / physiology
  • DNA Helicases / chemistry
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Replication / physiology*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • RNA, Small Interfering / genetics
  • Stress, Physiological / genetics*
  • Structure-Activity Relationship


  • Proliferating Cell Nuclear Antigen
  • RNA, Small Interfering
  • DNA Helicases
  • ZRANB3 protein, human