FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts.
Fanconi anemia (FA) is a heritable human cancer-susceptibility disorder, delineating a genetically heterogenous pathway for the repair of replication-blocking lesions such as interstrand DNA cross-links. Here we demonstrate that one component of this pathway, FANCJ, is a structure-specific DNA helicase that dissociates guanine quadruplex DNA (G4 DNA) in vitro. Moreover, in contrast with previously identified G4 DNA helicases, such as the Bloom's helicase (BLM), FANCJ unwinds G4 substrates with 5'-3' polarity. In the FA-J human patient cell line EUFA0030 the loss of FANCJ G4 unwinding function correlates with the accumulation of large genomic deletions in the vicinity of sequences, which match the G4 DNA signature. Together these findings support a role for FANCJ in the maintenance of potentially unstable genomic G/C tracts during replication.
London
Timothy B C
TB
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
Barber
Louise J
LJ
Mosedale
Georgina
G
Kelly
Gavin P
GP
Balasubramanian
Shankar
S
Hickson
Ian D
ID
Boulton
Simon J
SJ
Hiom
Kevin
K
D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D001667:Binding, Competitive; D002460:Cell Line; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004265:DNA Helicases / Q000378:metabolism*; D004261:DNA Replication; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism*; D054856:G-Quadruplexes; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D053484:RecQ Helicases / Q000378:metabolism*
C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D003432:Cross-Linking Reagents; D051856:Fanconi Anemia Complementation Group Proteins; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases