Transcription regulation through selective partitioning: Weak interactions with a strong foundation.

In this issue of Molecular Cell, De La Cruz, Pradhan, Veettil et al. examine how selective partitioning of proteins via low-affinity IDR-dependent interactions may help regulate RNA polymerase II (RNA Pol II) function and identify sequence features that drive partitioning in cells.

The BRCT domain of PARP1 binds intact DNA and mediates intrastrand transfer.

PARP1 is a key player in the response to DNA damage and is the target of clinical inhibitors for the treatment of cancers. Binding of PARP1 to damaged DNA leads to activation wherein PARP1 uses NAD to add chains of poly(ADP-ribose) onto itself and other nuclear proteins. PARP1 also binds abundantly to intact DNA and chromatin, where it remains enzymatically inactive.

Merging Established Mechanisms with New Insights: Condensates, Hubs, and the Regulation of RNA Polymerase II Transcription.

The regulation of RNA polymerase II (pol II) transcription requires a complex and context-specific array of proteins and protein complexes, as well as nucleic acids and metabolites. Every major physiological process requires coordinated transcription of specific sets of genes at the appropriate time, and a breakdown in this regulation is a hallmark of human disease. A proliferation of recent studies has revealed that many general transcription components, including sequence-specific, DNA-binding transcription factors, Mediator, and pol II itself, are capable of liquid-liquid phase separation, to form condensates that partition these factors away from the bulk aqueous phase.