**6. Acknowledgments**

This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. We thank M. Takado for critical reading of the manuscript.

### **7. References**


DNA-repair proteins are necessary for genome integrity. Their main functions are to control DNA repair and control the cell-cycle checkpoint. Recent studies have not clarified the role of DNA damage repair proteins in centrosome maintenance, although interactions between DNA-repair proteins and centrosomal proteins may have an important role in centrosome maintenance and microtubule regulation such as ATM/ATR-dependent CEP63 phosphorylation. How these interactions contribute to centrosome maintenance and microtubule regulation is unclear, so investigating the relationship between DNA-repair proteins and centrosomal proteins is important. Furthermore, the linkage between centrosome amplification and tumorigenesis is key to developing clinical targets. Inhibitors of the DNArepair protein PARP-1 and the centrosomal protein Aurora A could be a focus for anticancer drugs. Investigations into the molecular signaling pathway of DNA-repair proteins during

centrosome maintenance may contribute to advanced options for clinical therapeutics.

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**5. Conclusion** 

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**5** 

*USA* 

**Shared Regulatory Motifs in Promoters** 

*1School of Electrical Engineering and Computer Science, Ohio University, Athens, Ohio* 

This manuscript presents methods used to test, and resulting evidence to support the hypothesis that specialized transcription factor binding sites coordinate the expression of DNA repair genes. Building on the seminal work of the Elnitski laboratory (Yang et al. 2007), which identified the most complete set of human transcripts under the control of bidirectional promoters and identified the first putative regulatory networks that make use of the bidirectional promoter structure, the authors present additional details of these

Much of the work regarding the regulation of DNA repair proteins is aimed at the level of protein-protein interactions and post-translational processing events (Hurley et al. 2007, Jensen et al. 2011, Shibata et al. 2010). However, transcriptional activation of DNA repair genes is likely to utilize shared factors, especially in cases of induced activation, which have not been thoroughly evaluated. Yang, Koehly and Elnitski reported the discovery and characterization of 5,653 bidirectional promoters in the human genome (Yang et al. 2007). Prior to that date, bidirectional promoters were annotated only for protein-coding genes, and only 1,352 examples had been reported in the human genome. The work of Yang et al. included evidence from all noncoding-RNA genes, as well. Each bidirectional promoter regulates the expression of two genes, oriented in opposite directions with transcription start sites within 1000 bp of one another. The authors developed a novel approach to map all bidirectional promoters by analyzing the public expressed-sequence-tag (EST) data. The prevalence of this promoter structure led the authors to explore the hypothesis that it plays a role in regulation of certain classes of genes. They discovered that many more DNA repair genes have bidirectional promoters than previously reported and that many genes with somatic mutations in cancer have bidirectional promoters. The relevance of DNA repair genes to cancers (Kinsella et al. 2009, Liang et al. 2009, Smith et al. 2010, Kelley et al. 2008, Li et al. 2009, Bellizii et al. 2009, Naccarati et al. 2007, Berwick et al. 2000)) and the association of bidirectional promoters with DNA repair genes suggested that bidirectional promoters might indicate a higher-order type of regulatory structure that could be detected through common features at the DNA sequence level. If true, these features should discriminate bidirectional promoters and unidirectional promoters of genes with DNA repair functions.

**1. Introduction** 

regulatory networks.

Lonnie R. Welch1, Laura M. Koehly2 and Laura Elnitski3

*National Human Genome Research Institute, NIH, Bethesda, Maryland* 

*National Human Genome Research Institute, NIH, Bethesda, Maryland* 

**of Human DNA Repair Genes** 

*2Social and Behavioral Research Branch,* 

*3Genome Technology Branch* 

R. Hennekam, F. de Zegher, H.G. Dorr, and A. Reis. 2008. Mutations in the pericentrin (*PCNT*) gene cause primordial dwarfism. *Science*. 319:816–819.

