Entrez Summary: This gene plays a role in DNA interstrand cross-link repair and encodes a protein with 5' flap endonuclease and 5'-3' exonuclease activity. Mutations in this gene cause karyomegalic interstitial nephritis. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2016].
UniProt Summary: Nuclease required for the repair of DNA interstrand cross-links (ICL) recruited at sites of DNA damage by monoubiquitinated FANCD2. Specifically involved in repair of ICL- induced DNA breaks by being required for efficient homologous recombination, probably in the resolution of homologous recombination intermediates (PubMed:20603015, PubMed:20603016, PubMed:20603073, PubMed:20671156, PubMed:24981866, PubMed:25430771). Not involved in DNA double-strand breaks resection (PubMed:20603015, PubMed:20603016). Acts as a 5'-3' exonuclease that anchors at a cut end of DNA and cleaves DNA successively at every third nucleotide, allowing to excise an ICL from one strand through flanking incisions. Probably keeps excising with 3'-flap annealing until it reaches and unhooks the ICL (PubMed:25430771). Acts at sites that have a 5'-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3' flap (PubMed:25430771). Also has endonuclease activity toward 5'-flaps (PubMed:20603015, PubMed:20603016, PubMed:24981866). {ECO:0000269|PubMed:20603015, ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073, ECO:0000269|PubMed:20671156, ECO:0000269|PubMed:24981866, ECO:0000269|PubMed:25135477, ECO:0000269|PubMed:25430771}.
Pfam DomainsGO Terms
Pfam Domains
VRR NUC
GO Terms
flap-structured DNA binding
phosphodiesterase I activity
ubiquitin-dependent protein binding
5-flap endonuclease activity
5-3 exonuclease activity
nucleotide-excision repair, DNA incision
interstrand cross-link repair
intercellular bridge
double-strand break repair via homologous recombination
recombinational repair
nucleotide-excision repair
double-strand break repair
magnesium ion binding
DNA recombination
nucleic acid phosphodiester bond hydrolysis
DNA repair
DNA metabolic process
cellular response to DNA damage stimulus
cellular response to stress
CRISPR Data
Compound HitMost Correlated Genes in ChemogenomicsTissues where Essential in the Avana Dataset (DepMap 20Q1)