4RIA

FAN1 Nuclease bound to 5' phosphorylated nicked DNA

Summary for 4RIA

• Entry DOI: 10.2210/pdb4ria/pdb
• Related: 4RI8 4RI9 4RIB 4RIC 4RID
• Descriptor: Fanconi-associated nuclease 1, DNA (5'-D(P*AP*GP*CP*CP*AP*CP*GP*CP*CP*T)-3'), DNA (5'-D(P*AP*GP*AP*CP*TP*CP*CP*TP*C)-3'), ... (6 entities in total)
• Functional Keywords: nuclease, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q9Y2M0
• Total number of polymer chains: 10
• Total formula weight: 175560.66

Authors

Pavletich, N.P.,Wang, R. (deposition date: 2014-10-05, release date: 2014-12-10, Last modification date: 2024-02-28)

Primary citation

Wang, R.,Persky, N.S.,Yoo, B.,Ouerfelli, O.,Smogorzewska, A.,Elledge, S.J.,Pavletich, N.P.
DNA repair. Mechanism of DNA interstrand cross-link processing by repair nuclease FAN1.
Science, 346:1127-1130, 2014

PubMed 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.

PubMed: 25430771
DOI: 10.1126/science.1258973

Experimental method

X-RAY DIFFRACTION (3 Å)