Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN, USA.
Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Curr Genet. 2021 Oct;67(5):761-767. doi: 10.1007/s00294-021-01190-3. Epub 2021 May 7.
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.
RecQ 家族解旋酶存在于所有生命领域,在多个支撑基因组完整性的过程中发挥作用。因此,它们通常被称为基因组的守护者或管理者。然而,尽管它们很重要,但我们对它们在体内的基本功能仍知之甚少,也不完全了解它们在编码不止一种 RecQ 家族成员的生物体中是如何相互作用的。我们最近采用了多组学方法来更好地了解酿酒酵母 Hrq1 解旋酶及其与 Sgs1 的相互作用,这两种酶分别是与疾病相关的 RECQL4 和 BLM 解旋酶的功能同源物。通过合成遗传阵列分析、免疫沉淀结合质谱和 RNA-seq,我们发现 Hrq1 和 Sgs1 可能参与了许多超出其已知的经典 DNA 重组和修复功能的途径。例如,发现了与转录、核糖体生物发生和染色质/染色体组织之间的联系。本文简要介绍了这些最新结果,并提出了可能的后续实验。通过这种方式,我们希望全面了解这些 RecQ 解旋酶以及它们的突变如何导致基因组不稳定。