**7. Acknowledgement**

The author expresses her cordial thanks to Professor Joanna Deckert for her support and inspiration, to Anna Pastucha for her assistance with immunocytochemical assays employing anti-H3S10, and to Małgorzata Fronczak M.Sc. for her help in preparing this manuscript in English. This work was funded by the Ministry of Science and Higher Education, grant N N303 355935 (contract no. 3559/B/P01/2008/25).

#### **8. References**


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What are the practical implications and prospects of PCC induction? Could PCC induction serve as a novel anti-cancer approach? Undoubtedly, the phenomenon of premature mitosis is an essential characteristic of cell biology, therefore an important issue in respect of potential medical applications. It is so because, according to many researchers, the chemotherapy commonly used for the treatment of malignancy leads to extensive DNA damage, whereas PCC induction (resulting from the stimulation of biochemical mechanisms overriding the action of S-M checkpoint) can intensify therapeutic effects. Recently, druginduced PCC was optimized to assist analysis of the behavior of cancer cells with minimal side effects. However, PCC will also contribute to the understanding of normal cellular

The author expresses her cordial thanks to Professor Joanna Deckert for her support and inspiration, to Anna Pastucha for her assistance with immunocytochemical assays employing anti-H3S10, and to Małgorzata Fronczak M.Sc. for her help in preparing this manuscript in English. This work was funded by the Ministry of Science and Higher

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**A DNA Repair Protein BRCA1** 

Adisorn Ratanaphan *Prince of Songkla University* 

*Thailand* 

**as a Potentially Molecular Target for** 

**the Anticancer Platinum Drug Cisplatin** 

Cancer is a leading cause of death in the world. The incidence of cancers is related to environmental factors, behavioral patterns, and genetic disorders. Cancer therapy usually aims to selectively destroy cancer cells while sparing normal tissue. Most chemotherapeutic agents function by damaging cancer cell DNA. The cellular responses to DNA damage are thus critical factors for determining the effectiveness of most cancer therapies (Ashworth, 2008). When normal cells are exposed to damage, DNA repair mechanism is induced. The DNA repair processes are the cellular responses associated with the restoration of the normal DNA nucleotide sequences. The DNA repair activity of the cell is an important determinant of a cells sensitivity to chemotherapeutic agents. It is known that resistance to DNA-damaging agents can be associated with increased cellular repair activities, while defects in DNA repair pathways result in hypersensitivity to damage (Kelley & Fishel, 2008; Quinn et al., 2003, 2009). Several studies have clearly demonstrated that the impairment or absence of genes or proteins responsible for DNA damage repair, frequently causes genomic instability, cell cycle arrest and apoptosis. The importance of these repair pathways is highlighted by the fact that more than 100 genes have been found in mammalian cells that are involved in some way in DNA damage repair pathways. The breast cancer susceptibility gene 1 (*BRCA1*) is a tumor suppressor gene involved in maintaining genomic integrity through multiple functions in DNA damage repair, transcriptional regulation, a cell cycle checkpoint and protein ubiquitination (Brzovic et al., 2001; Hashizume et al., 2001; Mark et al., 2005; Varma et al., 2005; Williams et al., 2004). In cancer cells, damage to *BRCA1* by the anticancer platinum drug cisplatin may lead to a loss of such functions and ultimately results in cancer cell death. In addition, preclinical and clinical studies have recently revealed that inactivation of the BRCA1 protein in cancer cells leads to chemosensitivity. Therefore, approaching the BRCA1 protein as a potential therapeutic target for cisplatin or other such platinum based drugs might be of interest for molecular-targeted cancer therapy. In this chapter, the biophysical characterization and functional consequences of the human

*BRCA1* gene and the BRCA1 RING protein induced by cisplatin are described.

**2. Breast cancer susceptibility gene 1 (***BRCA1***) and its encoded protein** 

In 1990, chromosome 17q21 was identified by linkage analysis as the location of a breast cancer susceptibility gene 1 or *BRCA1* (Hall et al., 1990). The entire gene covers approximately 100 kb

**1. Introduction** 

Zhou B.-B.S. & Elledge S.J. (2000) The DNA damage response: putting checkpoints in perspective. *Nature* 408, 433-439. **12** 
