Kae1 of Saccharomyces cerevisiae KEOPS complex possesses ADP/GDP nucleotidase activity.

The KEOPS complex is an evolutionarily conserved protein complex in all three domains of life (Bacteria, Archaea, and Eukarya). In budding yeast Saccharomyces cerevisiae, the KEOPS complex (ScKEOPS) consists of five subunits, which are Kae1, Bud32, Cgi121, Pcc1, and Gon7. The KEOPS complex is an ATPase and is required for tRNA N6-threonylcarbamoyladenosine modification, telomere length maintenance, and efficient DNA repair. Here, recombinant ScKEOPS full complex and Kae1-Pcc1-Gon7 and Bud32-Cgi121 subcomplexes were purified and their biochemical activities were examined. KEOPS was observed to have ATPase and GTPase activities, which are predominantly attributed to the Bud32 subunit, as catalytically dead Bud32, but not catalytically dead Kae1, largely eliminated the ATPase/GTPase activity of KEOPS. In addition, KEOPS could hydrolyze ADP to adenosine or GDP to guanosine, and produce PPi, indicating that KEOPS is an ADP/GDP nucleotidase. Further mutagenesis characterization of Bud32 and Kae1 subunits revealed that Kae1, but not Bud32, is responsible for the ADP/GDP nucleotidase activity. In addition, the Kae1V309D mutant exhibited decreased ADP/GDP nucleotidase activity in vitro and shortened telomeres in vivo, but showed only a limited defect in t6A modification, suggesting that the ADP/GDP nucleotidase activity of KEOPS contributes to telomere length regulation.

Clinical and dermoscopic features of surgically treated melanocytic nevi: a retrospective study of 1046 cases.

BACKGROUND: Compared with Caucasians, unique demographic and clinical features have been reported in Chinese patients with malignant melanoma, but similar comparative studies of melanocytic nevi (MN) are lacking. This study examined the clinical and dermoscopic features of MN in surgically treated Chinese cases. METHODS: Clinical data and dermoscopic findings from 1046 cases of MN were collected and analyzed. Cases were treated from January 1 to December 31, 2014 at the Department of Dermatology and Venerology, Peking University First Hospital. The association between nevi location and histologic subtypes was examined with Chi-squared test and univariate logistic regression. Chi-squared test was also used to analyze the proportion of globular patterns across different body sites, and proportion of parallel furrow patterns across different histologic subtypes. RESULTS: The majority of the nevi were from female patients, irrespective of location. The range of age at the time of nevi onset was from 0 (birth) to 79 years. There were 381 (36.4%, 381/1046) congenital nevi; of these 81.6% (311/381) were present at birth. Nevi appeared before 30 years of age in 83.2% (870/1046) of the cases. Median values of length growth rate in congenital and acquired MN were 2.0 and 1.6, respectively. Median values of length growth rates in four age groups (0-9, 10-19, 20-29, and ≥30 years) of congenital nevi were 2.2, 2.0, 2.4, and 2.0, respectively. In acral nevi, which often need to be differentiated from acral lentiginous melanoma, 50.2% (109/217) were junctional (odds ratio [OR]; 95% confidence interval [CI]: 91.572 [52.210-160.959], P < 0.05). Acral location was also associated with a higher likelihood of compound nevi subtype (OR [95% CI]: 14.468 [8.981-23.306], P < 0.05). The globular (59.4%, 354/596) and pseudonetwork (48.8%, 291/596) dermoscopic patterns were often seen in the head and neck region. In areas other than head and neck and acral regions, the globular pattern was the commonest pattern (34.8%, 71/204) regardless of age. Parallel furrow pattern occurred in 46.0% (87/189) of acral MN, followed by fibrillar pattern (21.7%, 41/189). CONCLUSION: Unique clinical and dermoscopic features exist in Chinese patients with MN compared with observations reported in other population.