Abstract Liquid–liquid phase separation is a key phenomenon in the regulation of transcription in eukaryotes, leading to the formation of so-called membraneless organelles. While transcription factors take part in several types of membraneless organelles, it remains unclear how specific DNA binding, multivalent interactions with DNA/RNA, and condensation are interlinked. Here, we show that the NAC domain of suppressor of gamma response 1 (SOG1) (SOG1NAC), a transcription factor that is central to the DNA damage response in plants, can undergo liquid–liquid phase separation in vitro in the presence of both RNA or double-stranded DNA. This behaviour and the ability of SOG1NAC to bind DNA in a sequence-specific manner are dependent on its potential to form homodimers and the presence of a cluster of positive charges in its DNA-binding site. Short double-stranded DNA fragments containing the sequence motif that is specifically recognized by SOG1NAC inhibit RNA-mediated phase separation, suggesting overlapping binding sites for DNA and RNA. This may reflect a complex interplay between DNA and RNA binding that could control the formation of condensates at transcription sites.
Mignon et al. (Wed,) studied this question.