Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA.
Fanconi anaemia (FA) is an autosomal recessive disorder characterized by a diversity of clinical symptoms including skeletal abnormalities, progressive bone marrow failure and a marked predisposition to cancer. FA cells exhibit chromosomal instability and hyper-responsiveness to the clastogenic and cytotoxic effects of bifunctional alkylating (cross-linking) agents, such as diepoxybutane (DEB) and mitomycin C (MMC). Five complementation groups (A-E) have been distinguished on the basis of somatic cell hybridization experiments, with group FA-A accounting for over 65% of the cases analysed. A cDNA for the group C gene (FAC) was reported and localized to chromosome 9q22.3 (ref.8). Genetic map positions were recently reported for two more FA genes, FAA (16q24.3) and FAD (3p22-26). Here we report the isolation of a cDNA representing the FAA gene, following an expression cloning method similar to the one used to clone the FAC gene. The 5.5-kb cDNA has an open reading frame of 4,368 nucleotides. In contrast to the 63-kD cytosolic protein encoded by the FAC gene, the predicted FAA protein (M(r) 162, 752) contains two overlapping bipartite nuclear localization signals and a partial leucine zipper consensus, which are suggestive of a nuclear localization.
Department of Human Genetics, Free University, Amsterdam, The Netherlands.
J R
JR
Lo Ten Foe
M A
MA
Rooimans
L
L
Bosnoyan-Collins
N
N
Alon
M
M
Wijker
L
L
Parker
J
J
Lightfoot
M
M
Carreau
D F
DF
Callen
A
A
Savoia
N C
NC
Cheng
C G
CG
van Berkel
M H
MH
Strunk
J J
JJ
Gille
G
G
Pals
F A
FA
Kruyt
J C
JC
Pronk
F
F
Arwert
M
M
Buchwald
H
H
Joenje
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods*; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D015870:Gene Expression; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D011506:Proteins