Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division.
BRCA2 is responsible for familial breast and ovarian cancer, and its gene product is linked to DNA repair and transcriptional regulation. The BRCA2 protein exists mainly in the nucleus. Here, we show that BRCA2 has a centrosomal localization signal (CLS), localizes also to centrosomes during S and early M phases, and may regulate duplication and separation of the centrosomes. Green fluorescent protein (GFP) fused to the CLS peptides from BRCA2 (GFP-CLS) localizes to centrosomes and prevents endogenous BRCA2 from localizing to centrosomes. In addition, expression of GFP-CLS in cells leads to the abnormal duplication and positioning of centrosomes, resulting in the generation of multinuclear cells. These results thus implicate BRCA2 in the regulation of the centrosome cycle, and provide new insight into the aneuploid nature of many breast cancers.
Nakanishi
Akira
A
Department of Genetic Diagnosis, The Cancer Institute, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan.
Han
Xiangzi
X
Saito
Hiroko
H
Taguchi
Keiko
K
Ohta
Yoshiyasu
Y
Imajoh-Ohmi
Shinobu
S
Miki
Yoshio
Y
D020121:5' Untranslated Regions; D000782:Aneuploidy; D024682:BRCA2 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure*; D018385:Centrosome / Q000648:ultrastructure*; D005260:Female; D015200:Fluoroimmunoassay; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics; D010957:Plasmids; D016196:S Phase
D020121:5' Untranslated Regions; D024682:BRCA2 Protein