Basic Medicine, Oncology, Molecular and Cellular Biology
Elucidation of Genome Instability Due to the Failure of Cell Division and DNA Damage Response
Medical Sciences Course
- Master / Doctoral Degree
- CHIBA, Natsuko
Professor, M.D. Ph.D.
natsuko.chiba.c7*tohoku.ac.jp (Please convert "*" into "@".)
- Regulatory mechanism of breast cancer-related molecules in mitosis
- Response of tumor suppressor molecules to DNA damage
tumor suppressor gene, mitosis, DNA damage response, hereditary cancer, centrosome regulation
cell biology, molecular biology, animal experiment
Five to seven percent of all breast cancers are inherited, and the two most important breast cancer susceptibility genes, BRCA1 and BRCA2, were identified by linkage analysis of familial breast cancer. Mutations of BRCA1 and BRCA2 have been found in 25% of hereditary breast cancer. Recently, these breast cancers are called Hereditary Breast and Ovarian Cancer Syndrome (HBOC). In addition to hereditary cancer, it has been reported that BRCA1 is involved in a subtype of sporadic breast cancer, Triple-negative breast cancer, and in chemosensitivity to various cancers.
BRCA1 is involved in many cellular processes, including DNA repair and centrosome regulation. Defects in the regulatory mechanisms of centrosome and DNA repair result in defective mitoses, chromosome segregation errors, and the accumulation of DNA damage. These are significant sources of genome instability, a hallmark of cancer.
Our research particularly focuses on the functions of BRCA1 in DNA repair and centrosome regulation. To analyze the functions of BRCA1 and its related proteins, we perform cytological analyses, analyses using genetically modified mice, and analyses of clinical specimens. This research will contribute to the further understanding of carcinogenesis and aid in developing novel cancer therapies.
Figure 1. Dysfunction of BRCA1 causes cancer
Figure 2. OLA1 localizes to centrosome and spindle poles
- Matsuzawa A, Kanno S, Nakayama M, Mochiduki H, Wei L, Shimaoka T, Furukawa Y, Kato K, Shibata S, Yasui A, Ishioka C, and Chiba N. The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation. Molecular Cell, 53,101-114, 2014
- Kais Z, Chiba N, Ishioka C, Parvin J D. Functional differences among BRCA1 missense mutations in the control of centrosome duplication. Oncogene, 31(6): 799-804 2012
- Wei L, Lan L, Yasui A, Tanaka K, Saijo M, Matsuzawa A, Kashiwagi R, Maseki E, Hu Y, Parvin J D, Ishioka C and Chiba N. BRCA1 contributes to transcription-coupled repair of DNA damage through polyubiquitination and degradation of Cockayne syndrome B protein. Cancer Science, 102(10): 1840-1847, 2011
- Ransburgh D*, Chiba N*, Ishioka C, Toland A, and Parvin J D. (*co-first author) Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination. Cancer Res., 70(3): 988-995, 2010
- Wei L, Lan L, Hong Z, Yasui A, Ishioka C, and Chiba N. Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80. Mol. Cell. Biol. 28(24);7380-93, 2008