FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts

TY - JOUR

T1 - FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts

AU - London, Timothy B. C.

AU - Barber, Louise J.

AU - Mosedale, Georgina

AU - Kelly, Gavin P.

AU - Balasubramanian, Shankar

AU - Hickson, Ian D.

AU - Boulton, Simon J.

AU - Hiom, Kevin

PY - 2008/12/26

Y1 - 2008/12/26

N2 - 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.

AB - 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.

KW - Basic-Leucine Zipper Transcription Factors

KW - Binding, Competitive

KW - Cell Line

KW - Cell Line, Tumor

KW - Cross-Linking Reagents

KW - DNA Helicases

KW - DNA Replication

KW - Fanconi Anemia Complementation Group Proteins

KW - G-Quadruplexes

KW - Gene Deletion

KW - Genetic Predisposition to Disease

KW - Genome

KW - Humans

KW - Nucleic Acid Conformation

KW - Nucleic Acid Hybridization

KW - RecQ Helicases

UR - https://www.scopus.com/pages/publications/61349135721

U2 - 10.1074/jbc.M808152200

DO - 10.1074/jbc.M808152200

M3 - Article

C2 - 18978354

SN - 0021-9258

VL - 283

SP - 36132

EP - 36139

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 52

ER -