Abstract
The BRCA2 gene is involved in recombinational DNA repair and cytokinesis. BRCA2 defects are associated with chromosomal abnormalities, which is a hallmark of genomic instability that contributes to tumorigenesis. Here, we show that downregulation of a BRCA2 interacting protein (BCCIP) in HT1080 cells leads to chromosomal polyploidization, centrosome amplification and abnormal mitotic spindle formation. The BCCIP knockdown cells can enter mitosis and retain spindle checkpoint, but fail to complete cytokinesis. Our data suggest an essential role of BCCIP in the maintenance of genomic integrity.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Andreassen PR, Lohez OD, Lacroix FB, Margolis RL . (2001). Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol Biol Cell 12: 1315–1328.
Daniels MJ, Wang Y, Lee M, Venkitaraman AR . (2004). Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2. Science 306: 876–8769.
Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF . (1996). Abnormal centrosome amplification in the absence of p53. Science 271: 1744–1747.
Geddis AE, Kaushansky K . (2004). Megakaryocytes express functional Aurora-B kinase in endomitosis. Blood 104: 1017–1024.
Hans F, Dimitrov S . (2001). Histone H3 phosphorylation and cell division. Oncogene 20: 3021–3027.
Jallepalli PV, Waizenegger IC, Bunz F, Langer S, Speicher MR, Peters JM et al. (2001). Securin is required for chromosomal stability in human cells. Cell 105: 445–457.
Lengauer C, Kinzler KW, Vogelstein B . (1998). Genetic instabilities in human cancers. Nature 396: 643–649.
Liu J, Yuan Y, Huan J, Shen Z . (2001). Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2. Oncogene 20: 336–345.
Lu H, Guo X, Meng X, Liu J, Allen C, Wray J et al. (2005). The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair. Mol Cell Biol 25: 1949–1957.
Maier D, Zhang Z, Taylor E, Hamou MF, Gratzl O, Van Meir EG et al. (1998). Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas. Oncogene 16: 3331–3335.
Margolis RL, Lohez OD, Andreassen PR . (2003). G1 tetraploidy checkpoint and the suppression of tumorigenesis. J Cell Biochem 88: 673–683.
Meng X, Liu J, Shen Z . (2003). Genomic structure of the human BCCIP gene and its expression in cancer. Gene 302: 139–146.
Meng X, Liu J, Shen Z . (2004a). Inhibition of G1 to S cell cycle progression by BCCIP beta. Cell Cycle 3: 343–348.
Meng X, Lu H, Shen Z . (2004b). BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1. Cell Cycle 3: 1457–1462.
Meng X, Yuan Y, Maestas A, Shen Z . (2004c). Recovery from DNA damage-induced G2 arrest requires actin-binding protein filamin-A/actin-binding protein 280. J Biol Chem 279: 6098–6105.
Meng X, Yue J, Liu Z, Shen Z . (2007). Abrogation of the transactivation activity of p53 by BCCIP down-regulation. J Biol Chem 282: 1570–1576.
Meraldi P, Honda R, Nigg EA . (2002). Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. Embo J 21: 483–492.
Merlo A . (2003). Genes and pathways driving glioblastomas in humans and murine disease models. Neurosurg Rev 26: 145–158.
Moynahan ME, Pierce AJ, Jasin M . (2001). BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell 7: 263–272.
Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL et al. (2004). Genetic pathways to glioblastoma: a population-based study. Cancer Res 64: 6892–6899.
Ono T, Kitaura H, Ugai H, Murata T, Yokoyama KK, Iguchi-Ariga SM et al. (2000). TOK-1, a novel p21Cip1-binding protein that cooperatively enhances p21-dependent inhibitory activity toward CDK2 kinase. J Biol Chem 275: 31145–31154.
Powell SN, Kachnic LA . (2003). Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene 22: 5784–5791.
Rasheed BK, Fuller GN, Friedman AH, Bigner DD, Bigner SH . (1992). Loss of heterozygosity for 10q loci in human gliomas. Genes Chromosomes Cancer 5: 75–82.
Roversi G, Pfundt R, Moroni RF, Magnani I, van Reijmersdal S, Pollo B et al. (2005). Identification of novel genomic markers related to progression to glioblastoma through genomic profiling of 25 primary glioma cell lines. Oncogene 25: 1571–1583.
Rudkin TM, Foulkes WD . (2005). BRCA2: breaks, mistakes and failed separations. Trends Mol Med 11: 145–148.
Shinmura K, Bennett RA, Tarapore P, Fukasawa K . (2006). Direct evidence for the role of centrosomally localized p53 in the regulation of centrosome duplication. Oncogene (E-pub 30 Oct 2006).
Tarapore P, Fukasawa K . (2002). Loss of p53 and centrosome hyperamplification. Oncogene 21: 6234–6240.
Tarapore P, Horn HF, Tokuyama Y, Fukasawa K . (2001). Direct regulation of the centrosome duplication cycle by the p53-p21Waf1/Cip1 pathway. Oncogene 20: 3173–3184.
Venkitaraman AR . (2002). Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108: 171–182.
Acknowledgements
This research was supported by National Institute of Health grants CA115488 and ES08353 and by the US Army Medical Research and Materiel Command grants DAMD17-02-1-0515 and DAMD17-03-1-0317. We thank the technical support from the flow cytometry and the fluorescence microscopy facility of UNM Cancer Research and Treatment Center.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on the Oncogene Web site (http://www.nature.com/onc).
Supplementary information
Rights and permissions
About this article
Cite this article
Meng, X., Fan, J. & Shen, Z. Roles of BCCIP in chromosome stability and cytokinesis. Oncogene 26, 6253–6260 (2007). https://doi.org/10.1038/sj.onc.1210460
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1210460
Keywords
This article is cited by
-
Identification of microRNA signature in the progression of gestational trophoblastic disease
Cell Death & Disease (2018)
-
Roles of BCCIP deficiency in mammary tumorigenesis
Breast Cancer Research (2017)
-
High Expression of BCCIP β Can Promote Proliferation of Esophageal Squamous Cell Carcinoma
Digestive Diseases and Sciences (2017)
-
Human INO80/YY1 chromatin remodeling complex transcriptionally regulates the BRCA2- and CDKN1A-interacting protein (BCCIP) in cells
Protein & Cell (2016)
-
Expression pattern of BCCIP in hepatocellular carcinoma is correlated with poor prognosis and enhanced cell proliferation
Tumor Biology (2016)
