**2. Centrosomes and aneuploidy**

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 chromosome segregation (Godinho et al., 2009).

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 aneuploidy.

The Potential Roles of DNA-Repair Proteins in Centrosome Maintenance 59

(A) Two centrosomes separate at the two poles, and normal cell division progresses. (B) Overduplicated centrosomes accumulate into the two poles and form a pseudo-bipolar spindle, leading to improper cell division and chromosome instability. (C) Overduplicated centrosomes form a multipolar spindle,

also contributes to abrogation of the linkage between the cell cycle and the centrosome duplication cycle because the p53-dependent G2/M checkpoint is activated in an ataxia telangiectasia mutated (ATM)/ATM- and Rad3-related (ATR)-dependent manner after

DNA-repair-related proteins, including ATM, ATR, checkpoint kinase 1 (CHK1), CHK2, PARP1, Nijmegen breakage syndrome (NBS1), BRCA1, BRCA2, RAD51, RAD51 paralogs,

Fig. 2. Cell division during mitosis with normal and abnormal number of centrosomes.

leading to a failure of cytokinesis and mitotic catastrophe.

**4. Centrosomes and DNA-repair proteins** 

DNA damage such as from irradiation.

Centrosomes are located at the periphery of the nucleus and consist of a mother centriole and a daughter centriole, surrounded by the pericentriolar material (PCM). The γ-tubulin ring complex (γ-TuRC) binds to the PCM to form microtubules.

Fig. 1. Centrosome structure.
