The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia.
Seven Fanconi anemia-associated proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCL) form a nuclear Fanconi anemia core complex that activates the monoubiquitination of FANCD2, targeting FANCD2 to BRCA1-containing nuclear foci. Cells from individuals with Fanconi anemia of complementation groups D1 and J (FA-D1 and FA-J) have normal FANCD2 ubiquitination. Using genetic mapping, mutation identification and western-blot data, we identify the defective protein in FA-J cells as BRIP1 (also called BACH1), a DNA helicase that is a binding partner of the breast cancer tumor suppressor BRCA1.
Levran
Orna
O
Laboratory for Human Genetics & Hematology, The Rockefeller University, New York, New York, USA.
Attwooll
Claire
C
Henry
Rashida T
RT
Milton
Kelly L
KL
Neveling
Kornelia
K
Rio
Paula
P
Batish
Sat Dev
SD
Kalb
Reinhard
R
Velleuer
Eunike
E
Barral
Sandra
S
Ott
Jurg
J
Petrini
John
J
Schindler
Detlev
D
Hanenberg
Helmut
H
Auerbach
Arleen D
AD
D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus; D002886:Chromosomes, Human, Pair 17; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D020365:RNA Helicases / Q000235:genetics* / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; C499905:FANCD2 protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D025801:Ubiquitin; C000618935:BRIP1 protein, human; D020365:RNA Helicases