For example mapping strand breaks and comparing WZ4002 repair in transcribed and nontranscribed regions. Such studies may be relevant to the repair of DNA in genomic chromatin in view of the topological similarity of the minichromosome to chromatin loops and its position in regions of lower chromatin density within the nucleus where double strand breaks in genomic DNA and sites of their repair are predominantly localised. Prostate cancers usually present as androgen-dependent tumors, susceptible to growth arrest/apoptosis induced by androgen ablation therapy. Although initially effective, androgen ablation frequently leads to the PF-4217903 development of castration-resistant prostate cancer, which is generally also resistant to other available treatments. As such, castration resistance commonly marks the end stage form of prostate cancer and is the major obstacle in disease management. Development of castration-resistant prostate cancer is characteristically associated with marked increases in resistance to apoptosis, a major death pathway for drug action. Apoptosis resistance resulting from up-regulation of antiapoptotic genes and their products is thought to be a key contributor in the development of castration resistance, as well as general resistance to anti-cancer treatments. Elucidating the role of anti-apoptotic genes/proteins in the progression of prostate cancer is therefore likely to lead to improvements in the treatment of refractory disease. The Inhibitors of Apoptosis Protein family has been reported to play a role in apoptosis resistance in a variety of cancer cell lines and is characterized by the presence in the proteins of one to three copies of a Baculoviral IAP Repeat domain. The IAPs have been demonstrated to bind to and inhibit a variety of pro-apoptotic factors, thereby effectively suppressing apoptosis induced by a wide range of effectors, including chemotherapeutics and irradiation. The BIR domain is essential for interaction of the IAPs with pro-apoptotic factors, including caspases. The caspases are a family of cysteineaspartic acid-specific proteases, present in a pro-form which, once activated via cleavage, is responsible for degradation of death substrates such as poly-ADP-ribose polymerase thereby triggering apoptosis. Cleaved caspase-3 and cleaved PARP can be readily detected by Western blot analysis and are commonly used as markers for apoptosis. Apoptosis is often associated with autophagy, a process involving lysosomal degradation of a cell��s own components. It involves packaging of proteins and organelles within autophagosomes, followed by fusion with lysosomes leading to degradation of the proteins and organelles. The role of autophagy in the development of cancer and its treatment is complex, since there is evidence that autophagy can promote and suppress cancer growth. Inhibition of autophagy by disruption of essential autophagy genes has been shown to promote tumorigenesis and hence autophagy can have a tumor-suppressive effect. However, there is increasing evidence that autophagy can act as a survival mechanism for cancer cells in response to a wide range of stresses, including treatment with anti-cancer agents. To detect autophagic activity in cultured cells, Western blot detection of LC3B-II is often used. LC3B-II is specifically associated with autophagosomes and levels of LC3B-II have been demonstrated to correlate with the number of autophagosomes within cells. However, since LC3B-II is degraded upon autophagosome-lysosome fusion.