Aging and cancer cell biology, 2009

Cancer is an age‐related disease in organisms with renewable tissues. A malignant tumor arises in part from genomic damage, which can also drive age‐related degeneration. However, cancer differs from many age‐related degenerative diseases in that it entails gain‐of‐function changes that confer new (albeit aberrant) properties on cells, resulting in vigorous cell proliferation and survival. Nonetheless, interventions that delay age‐related degeneration – for example, caloric restriction or dampened insulin/IGF‐1 signaling – often also delay cancer. How then is the development of cancer linked to aging? The answer to this question is complex, as suggested by recent findings. This Hot Topic review discusses some of these findings, including how genomic damage might alter cellular properties without conferring mutations, and how some genes that regulate lifespan in organisms that lack renewable tissues might affect the development of cancer in mammals.     

Immunology and molecular biology of Echinococcus infections

Echinococcus spp. are the etiological agents of hydatid disease in man and other intermediate hosts. Many questions regarding the factors which determine susceptibility/resistance to hydatid disease, and the factors which influence the viability and fertility of hydatid cysts, remain to be answered. Recent research into the effects of hydatid infection on the immune system of the host has provided some insights into the host-parasite relationships. Immunochemical and recombinant DNA techniques are being applied to improve diagnosis of hydatidosis in man and E. granulosus infection in dogs, and also in the development of vaccines against infection with taeniid cestode larvae. The successes which have been achieved in these areas are likely to provide valuable tools for the control of cystic hydatidosis in man. These recent studies in the areas of immunobiology, serological diagnosis and vaccination are reviewed.     

Reproducibility and cell biology

Based on its in vitro unwinding activity on G-quadruplex (G4) DNA, the Bloom syndrome–associated helicase BLM is proposed to participate in telomere replication by aiding fork progression through G-rich telomeric DNA. Single molecule analysis of replicated DNA (SMARD) was used to determine the contribution of BLM helicase to telomere replication. In BLM-deficient cells, replication forks initiating from origins within the telomere, which copy the G-rich strand by leading strand synthesis, moved slower through the telomere compared with the adjacent subtelomere. Fork progression through the telomere was further slowed in the presence of a G4 stabilizer. Using a G4-specific antibody, we found that deficiency of BLM, or another G4-unwinding helicase, the Werner syndrome-associated helicase WRN, resulted in increased G4 structures in cells. Importantly, deficiency of either helicase led to greater increases in G4 DNA detected in the telomere compared with G4 seen genome-wide. Collectively, our findings are consistent with BLM helicase facilitating telomere replication by resolving G4 structures formed during copying of the G-rich strand by leading strand synthesis.