News & Views in 2003

Identification of a new imprinting control element (ICE) on mouse chromosome 12 brings the total to five. Common features of imprinting mechanisms suggest a general model of ICE function.

Huntington disease is caused by a polyglutamine repeat expansion in the huntingtin protein. A new study highlights an important role for the normal protein in neuronal transcriptional regulation.

The technical problem of detecting the retrotransposition—amplification and genomic dispersion of sequences through an RNA intermediate—of Pol III–directed transcripts has been solved. This provides a long-sought experimental system to learn how Alu repeats amplified to a high copy number in human DNA.

The cyclin E–CDK2 complex was thought to be an essential regulator of the mitotic cell cycle. Surprisingly, disabling the critical genes in the mouse has fewer effects than anticipated.

Breaking the bond between an enhancer and a promoter has serious biological consequences. A recent study describes a new chromatin insulator in the Drosophila melanogaster Antennapedia complex (ANTC) that may ensure that nearby enhancers remain faithful to their respective promoters.

A new study of Drosophila melanogaster bridges the gap between quantitative trait loci (QTLs) for lifespan and a gene involved in catecholamine synthesis. The causative gene also contributes to variation in lifespan in a natural population and seems to be subject to balancing selection in nature.

Quantitative modifiers of neoplastic pathways are greatly treasured but difficult to identify at the molecular level. An apparent success has now identified a centrosomal protein kinase that affects many cancer histotypes.

Nephronophthisis is the most common inherited cause of renal failure in children. Two new studies add to the growing body of literature that suggests that cilial dysfunction may underlie all forms of cystic renal disease.

The molecular pathogenesis of most forms of amyotrophic lateral sclerosis (ALS) is poorly understood. Now, reduced expression of vascular endothelial growth factor (VEGF) is shown to be a risk factor for contracting ALS. Addition of Vegf in mice is shown to protect motoneurons from damage.

An analysis of the propinquity of selected gene loci in the nuclei of a particular lymphoblastoid cell line has identified a statistical correlation with their propensity for oncogenic translocations.

Muscle mitochondrial respiratory metabolism is reduced in aging and diabetes. Now, coordinated changes in expression of genes involved in oxidative phosphorylation have been found in individuals with type 2 diabetes mellitus (DM2). Peroxisome proliferator activator protein-γ co-activator-1α (PGC-1α) seems to be in charge of this orchestrated change in gene expression.

The human Y chromosome is the first constitutively haploid metazoan chromosome to be sequenced. It has a unique genomic landscape with a complex evolutionary history that has endowed it with few genes but many nearly identical dispersed repeats that underlie the structural fluidity of this unusual chromosome.

Adeno-associated virus (AAV) holds much promise as a vector for gene therapy. Although transgene expression usually occurs from extrachromosomal vector genomes, vectors occasionally integrate into the host genome. A new study in normal mammalian cells shows that the insertions are associated with genomic deletions and occur preferentially in actively transcribed genes.

The direct inhibition of DNA mismatch repair by cadmium provides a molecular mechanism for cadmium toxicity with profound implications for human health, risk assessment and biological understanding of environmental mutagens. Alteration of key DNA damage response pathways may prove even more important than direct DNA damage by mutagens.