The conserved histone chaperone Spt6 is strongly required for DNA replication and genome stability

• Published in: Cell reports (Cambridge) 2023-03, Vol.42 (3), p.112264-112264, Article 112264
• Main Authors: Miller, Catherine L.W., Winston, Fred
• Format: Article
• Language: English
• Subjects: chromatin; Chromatin - metabolism; CP: Molecular biology; DNA replication; DNA Replication - genetics; genome stability; Genomic Instability; histone chaperones; Histone Chaperones - genetics; Histone Chaperones - metabolism; Histones - metabolism; Humans; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; spt6; Transcription, Genetic; Transcriptional Elongation Factors - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112264

Histone chaperones are an important class of proteins that regulate chromatin accessibility for DNA-templated processes. Spt6 is a conserved histone chaperone and key regulator of transcription and chromatin structure. However, its functions outside of these roles have been little explored. In this work, we demonstrate a requirement for S. cerevisiae Spt6 in DNA replication and, more broadly, as a regulator of genome stability. Depletion or mutation of Spt6 impairs DNA replication in vivo. Additionally, spt6 mutants are sensitive to DNA replication stress-inducing agents. Interestingly, this sensitivity is independent of the association of Spt6 with RNA polymerase II (RNAPII), suggesting that spt6 mutants have a transcription-independent impairment of DNA replication. Specifically, genomic studies reveal that spt6 mutants have decreased loading of the MCM replicative helicase at replication origins, suggesting that Spt6 promotes origin licensing. Our results identify Spt6 as a regulator of genome stability, at least in part through a role in DNA replication. [Display omitted] •Spt6 has been primarily studied as a histone chaperone important for transcription•Spt6 mutants exhibit genomic instability, consistent with DNA replication defects•Spt6 mutants are defective for DNA replication in vivo•The replication defect is likely at the initiation stage, during origin licensing Spt6 has been primarily studied for its roles during transcription. Miller and Winston show that it also has a role in DNA replication. They demonstrate that spt6 mutants are defective for replication in vivo, at least in part by defects in loading the MCM helicase complex, which is required for origin firing.