In this issue of Molecular Cell, Roy et al. (2021) and Belan demonstrate that the yeast nematode RAD51 paralog complexes function as chaperones to promote assembly nucleoprotein filament on RPA-coated ssDNA.

A n interphase meeting between X chromosomes, revealed by Na Xu, Chia-Lun Tsai, and Jeannie Lee (Harvard Medical School, Boston, MA), ensures that one and only one is silenced. Silencing of one of the two X chromosomes in a female somatic cell brings the gene dosage level down to that of male cells. Inactivation is controlled by several noncoding RNAs transcribed from, and acting in cis upon, t...

Wolfram syndrome is an autosomal recessive disorder caused by mutations in WFS1 and is characterized by insulin-dependent diabetes mellitus, optic atrophy, and deafness. To investigate the cause of β-cell failure, we used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. WFS1-deficient β-cells showed increased levels of endoplasmic reticulu...

Sepsis-induced lymphopenia is a major cause of morbidities in intensive care units and in populations with chronic conditions such as renal failure, diabetes, HIV and alcohol abuse. Currently, other than supportive care and antibiotics, there are no treatments for this condition. We developed an in vitro assay to understand the role of the ER-stress-mediated apoptosis process in lymphocyte deat...

Folding of many cellular proteins is facilitated by molecular chaperones. Analysis of both prokaryotic and lower eukaryotic model systems has revealed the presence of ribosome-associated molecular chaperones, thought to be the first line of defense against protein aggregation as translating polypeptides emerge from the ribosome. However, structurally unrelated chaperones have evolved to carry o...

Hsp70 chaperones play a role in polyoma- and papillomavirus assembly, as evidenced by their interaction in vivo with polyomavirus capsid proteins at late times after virus infection and by their ability to assemble viral capsomeres into capsids in vitro. We studied whether Hsp70 chaperones might also participate in the uncoating reaction. In vivo, Hsp70 co-immunoprecipitated with polyomavirus v...

Chaperones are the primary regulators of the proteostasis network and are known to facilitate protein folding, inhibit protein aggregation, and promote disaggregation and clearance of misfolded aggregates inside cells. We have tested the effects of five chaperones on the toxicity of misfolded oligomers preformed from three different proteins added extracellularly to cultured cells. All the chap...

The way in which a newly synthesized polypeptide chain folds into its unique three-dimensional structure remains one of the fundamental questions in molecular biology. Protein folding in the cell is a problematic process and, in many cases, requires the assistance of a network of molecular chaperones to support productive protein foldingin vivo. During protein biosynthesis, ribosome-associated ...

Type III secretion (TTS) systems are used by many Gram-negative pathogens to inject virulence proteins into the cells of their hosts. Several of these virulence effectors require TTS chaperones that maintain them in a secretion-competent state. Whereas most chaperones bind only one effector, Spa15 from the human pathogen Shigella flexneri and homologous chaperones bind several seemingly unrelat...