Summary information and primary citation
- PDB-id
-
4ri9;
DSSR-derived features in text and
JSON formats
- Class
- hydrolase-DNA
- Method
- X-ray (2.9 Å)
- Summary
- Fan1 nuclease bound to 5' phosphorylated
p(dt)-3'(dt-dt-dt-dt-dt-dt-dt-dt) double flap DNA
- Reference
-
Wang R, Persky NS, Yoo B, Ouerfelli O, Smogorzewska A,
Elledge SJ, Pavletich NP (2014): "DNA
repair. Mechanism of DNA interstrand cross-link
processing by repair nuclease FAN1."
Science, 346, 1127-1130. doi:
10.1126/science.1258973.
- Abstract
- DNA interstrand cross-links (ICLs) are highly toxic
lesions associated with cancer and degenerative diseases.
ICLs can be repaired by the Fanconi anemia (FA) pathway and
through FA-independent processes involving the FAN1
nuclease. In this work, FAN1-DNA crystal structures and
biochemical data reveal that human FAN1 cleaves DNA
successively at every third nucleotide. In vitro, this
exonuclease mechanism allows FAN1 to excise an ICL from one
strand through flanking incisions. DNA access requires a
5'-terminal phosphate anchor at a nick or a 1- or
2-nucleotide flap and is augmented by a 3' flap, suggesting
that FAN1 action is coupled to DNA synthesis or
recombination. FAN1's mechanism of ICL excision is well
suited for processing other localized DNA adducts as
well.
