rst systematic study to quantitatively PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19639295 assess interactions between Fe chelators and established chemotherapeutic agents using breast cancer cells. The Sunset Yellow FCF combinations led to antagonism, but also synergism, with the effects observed being dose-dependent. Collectively, our results indicate that synergistic interactions are observed with combinations of the lipophilic chelators, NHAPI or Dp44mT, with DOX and also the combinations of SIH, NHAPI or Dp44mT with TMX. Furthermore, our data encourage further research of the combination potential of TMX with Fe chelation and strengthen the hypothesis regarding the Fe estrogen link in breast cancer. The results are important for on-going preclinical studies with these novel Fechelating agents and also for future clinical trials. The essential functions of telomeres are to promote complete replication of the chromosome terminus and to distinguish the natural ends of chromosomes from DNA double-strand breaks. Telomeres consist of simple G-rich repeat DNA that is synthesized and maintained by the telomerase reverse transcriptase. Telomerase docks on the 39 single-strand extension on the chromosome end via contacts with telomere binding proteins. The two main telomere protein complexes are shelterin and CST. Vertebrate shelterin is composed of six core subunits including the double-strand DNA binding TRF1 and TRF2. Although the CST complex, which associates with the G-overhang, was first identified in budding yeast, CST-related components have now been identified in Schizosaccharomyces pombe, vertebrates, and plants. Arabidopsis thaliana encodes at least six TRF-like proteins, but CST seems to be the primary factor required for telomere integrity. Loss of any of the three CST proteins in plants leads to dramatic telomere shortening, end-to-end chromosome fusions and severe developmental defects that culminate in stem cell failure. In vertebrates, shelterin plays a more significant role in promoting telomere stability than CST, which acts primarily to facilitate telomeric DNA replication. Thus, while core components of the telomere complex are conserved, their specific contributions to telomere biology are evolving. Curiously, although a major function of telomeres is to distinguish chromosome ends from DNA damage, multiple DNA repair-related proteins are vital for normal telomere function. The phosphoinositide-3-kinase-related protein kinase ATM responds to DSBs, and yet is required for telomerase action at chromosome ends. Likewise, the related kinase ATR, which is activated by ssDNA breaks, is implicated in telomerase recruitment as well as promoting DNA replication through the ds portion of the telomere. The Ku70/80 heterodimer is required for the classic nonhomologous end joining pathway of DSB repair, but also has multiple functions at telomeres. Ku protects chromosome ends, particularly 
the extreme 59 terminus. Ku also interacts with the telomerase RNA subunit and recruits telomerase to budding yeast telomeres in the G1 phase of the cell cycle. Another group of repair-related proteins required for telomere function in human cells are the poly polymerases . PARPs are found in all eukaryotic supergroups and catalyze the synthesis and transfer of poly ADP-ribose from NAD+ to target proteins. PARylation can alter the function PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19637192 of proteins in several ways. It adds a negative charge to proteins and can cause a protein to dissociate from its binding PARP Function at Plant Telomeres partner, often DNA, a
