A deep dive into the RecQ interactome: something old and something new.

ABSTRACT

RecQ family helicases are found in all domains of life and play roles in multiple processes that underpin genomic integrity. As such, they are often referred to as guardians or caretakers of the genome. Despite their importance, however, there is still much we do not know about their basic functions in vivo, nor do we fully understand how they interact in organisms that encode more than one RecQ family member. We recently took a multi-omics approach to better understand the Saccharomyces cerevisiae Hrq1 helicase and its interaction with Sgs1, with these enzymes being the functional homologs of the disease-linked RECQL4 and BLM helicases, respectively. Using synthetic genetic array analyses, immuno-precipitation coupled to mass spectrometry, and RNA-seq, we found that Hrq1 and Sgs1 likely participate in many pathways outside of the canonical DNA recombination and repair functions for which they are already known. For instance, connections to transcription, ribosome biogenesis, and chromatin/chromosome organization were uncovered. These recent results are briefly detailed with respect to current knowledge in the field, and possible follow-up experiments are suggested. In this way, we hope to gain a wholistic understanding of these RecQ helicases and how their mutation leads to genomic instability.