Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell. 2011 Apr 15;145(2):198-211. doi: 10.1016/j.cell.2011.03.004.

Human flap endonuclease structures, DNA double-base flipping, and a unified understanding of the FEN1 superfamily.

Author information

  • 1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Abstract

Flap endonuclease (FEN1), essential for DNA replication and repair, removes RNA and DNA 5' flaps. FEN1 5' nuclease superfamily members acting in nucleotide excision repair (XPG), mismatch repair (EXO1), and homologous recombination (GEN1) paradoxically incise structurally distinct bubbles, ends, or Holliday junctions, respectively. Here, structural and functional analyses of human FEN1:DNA complexes show structure-specific, sequence-independent recognition for nicked dsDNA bent 100° with unpaired 3' and 5' flaps. Above the active site, a helical cap over a gateway formed by two helices enforces ssDNA threading and specificity for free 5' ends. Crystallographic analyses of product and substrate complexes reveal that dsDNA binding and bending, the ssDNA gateway, and double-base unpairing flanking the scissile phosphate control precise flap incision by the two-metal-ion active site. Superfamily conserved motifs bind and open dsDNA; direct the target region into the helical gateway, permitting only nonbase-paired oligonucleotides active site access; and support a unified understanding of superfamily substrate specificity.

Copyright © 2011 Elsevier Inc. All rights reserved.

Comment in

PMID:
21496641
[PubMed - indexed for MEDLINE]
PMCID:
PMC3086263
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk