**8. Acknowledgements**

The author would like to thank the members of his research group for helpful discussions. The author also appreciates the help of Jan Martel during preparation of the manuscript. This review is partly supported by the National Science Council (Taiwan), Chang Gung University, and the Foundation for the Advancement of Outstanding Scholarship.

#### **9. References**


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The author would like to thank the members of his research group for helpful discussions. The author also appreciates the help of Jan Martel during preparation of the manuscript. This review is partly supported by the National Science Council (Taiwan), Chang Gung

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**1. Introduction** 

proteins in centrosome maintenance.

**2. Centrosomes and aneuploidy** 

chromosome segregation (Godinho et al., 2009).

aneuploidy.

**4** 

*Japan* 

**The Potential Roles of DNA-Repair** 

Mikio Shimada, Akihiro Kato and Junya Kobayashi

*Radiation Biology Center, Kyoto University* 

**Proteins in Centrosome Maintenance** 

The centrosome, an organelle that regulates microtubules, is necessary for proper cell division in mammalian cells (Doxsey, 2001; Nigg, 2002, 2007). The existence of centrosomes was first reported 100 years ago by Theodor Boveri (Boveri, 2008). A centrosome is composed of two centrioles and is surrounded by pericentriolar material (PCM), which provides a binding site for the γ-tubulin ring complex (γ-TuRC). The γ-TuRC acts as a microtubule nucleation template, and it attaches to the PCM to form microtubules (Fig. 1). The number of centrosomes is precisely regulated, and the duplication cycle is synchronized to the cell cycle. Centrosomes duplicate once in the S phase and mature in the G2 phase, and in the M phase, centrosomes are divided into daughter cells (Fig. 2). The number of centrosomes and their functions are regulated by many proteins including centrosome proteins, cell-cycle proteins, and DNA-repair proteins, and recently, the role of DNA-repair proteins in centrosome maintenance has been clarified. In this chapter, we introduce recent findings about the roles of DNA-repair

Many cancer cells possess extra centrosomes, which is called centrosome amplification and means overduplication of centrosomes. Extra centrosomes can lead to multipolar cell divisions, subsequent aneuploidy, and cell death (Kwon et al., 2008). Although almost all multipolar cell division results in cell death via mitotic catastrophe (Ganem et al., 2009), some multipolar cells divide into daughter cells to maintain aneuploidy. Aneuploidic cells are believed to potentially cause tumorigenesis. Recent studies suggest that aneuploidic cells are produced by a clustering of extra centrosomes, which accumulate at the two poles, and microtubules from each of the extra centrosomes attach to the chromosomes prior to mitosis (Kwon et al., 2008) (Fig. 2). The tension created by the extra centrosomes leads to improper

Several environmental factors and chemicals, or carcinogens, including ionizing radiation and benzopyrene, can induce extra centrosomes (Sato et al., 2000). Thus, failure of the centrosome duplication cycle could cause tumorigenesis via chromosome

