| Literature DB >> 21496641 |
Susan E Tsutakawa1, Scott Classen, Brian R Chapados, Andrew S Arvai, L David Finger, Grant Guenther, Christopher G Tomlinson, Peter Thompson, Altaf H Sarker, Binghui Shen, Priscilla K Cooper, Jane A Grasby, John A Tainer.
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.Entities:
Mesh：
Substances：
Year: 2011 PMID： 21496641 PMCID： PMC3086263 DOI： 10.1016/j.cell.2011.03.004
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582