Reviews & Analysis

Controlling the ability of retrotransposons to replicate and reinsert within the genome is important for maintaining the integrity of genetic information. For the first time, it has been shown that naturally occurring small interfering RNAs exist in human cells and derive from the L1 retrotransposon, providing evidence that RNA interference has a role in regulation of retrotransposition in humans.

The activity of a handful of transcription factors, such as mammalian NF-κB, Drosophila melanogaster Cubitus interruptus and yeast Spt23 and Mga2, are regulated through partial protein degradation by the proteasome. New data now show that the proteasome activates membrane-bound Spt23 and Mga2 by initiating their proteolysis at an internal site and then degrading the proteins bidirectionally toward both ends of the polypeptide chain, modifying our ideas on how the proteasome degrades targeted substrates.

Replication initiators in both bacteria and eukaryotes are AAA+ proteins that bind and remodel origin DNA sequences, preparing them for chromosome duplication. Two new reports show that the bacterial DnaA and eukaryotic ORC initiators form protein helical filaments. Wrapping of origin DNA around these filaments may promote DNA unwinding and subsequent assembly of replication forks.

A new crystal structure reveals the path taken by single-stranded (ss) DNA through the central channel of a hexameric helicase. The path resembles a spiral staircase and provides an answer to the question of how hexameric helicases translocate on ssDNA.

The main function of mouse POT1 proteins is to regulate G-overhang length, suppress telomere recombination and prevent a telomeric DNA-damage response. They are not needed to prevent G-overhang loss and have only a minor role in preventing telomere fusions.

Two new studies on the structure of an enzyme involved the synthesis of mammalian NAD shed new light on the evolutionary and biochemical complexity of this fundamental metabolic pathway.

Riboswitches provide an elegantly simple means of coupling metabolic sensing to genetic regulation. Recent work provides a wealth of structural insight into ligand binding by these RNAs.

Yeast RNA polymerase II has been proposed to 'scan' template DNA for transcription start sites. A new study mapping promoter DNA trajectory through the preinitiation complex suggests a mechanism for how this occurs.

SecA is an essential eubacterial protein in which the ATPase motor from DEAD-box RNA helicases has adapted to function as a processive polypeptide pump. A new report suggests that a disorder-order transition in the DEAD-box motor is responsible for distinctive thermodynamic features of SecA's conformationally coupled ATPase cycle.

Covalent modifications of histones play an important role in regulating chromatin structure and function, probably by serving as docking sites for effector proteins. The discovery that PHD fingers of two different proteins recognize trimethyl-Lys4 of histone H3 supports and extends this notion.

The crystal structure of the full-length yeast Hsp90 sheds new light on the conformational cycle and the functional regulation of this important molecular chaperone.

Since the discovery of Prp16, a spliceosomal ATPase that alters the fidelity of splicing, many other ATPases associated with the spliceosome have been postulated to work similarly. The finding that Prp22, a DEAH-box ATPase, functions as a fidelity factor for the second step of splicing supports this hypothesis.

The E2 enzymes for ubiquitin and SUMO conjugation share a conserved active site that has long been mysterious for lack of identifiable catalytic residues. In an elegant tour de force, it is now shown how three E2 residues not only position the target lysine but also substantially lower its pK to allow deprotonation and efficient substrate transfer.

A recent report identifies a cellular protein that recognizes inner nuclear membrane (INM) targeting signals. This finding provides the missing link for the transport of large inner nuclear membrane proteins as they travel from the cytosolic face of the endoplasmic reticulum to the INM.