Chromatin organisation plays a key role in basic cellular processes, such as transcription and DNA replication. The chromatin-associated protein scaffold attachment factor A (SAF-A) modulates chromatin structure and is known to promote open chromatin at transcriptionally active regions. However, its contribution to cell proliferation and DNA replication is unclear. Now, Shin-ichiro Hiraga and colleagues (Connolly et al., 2022) investigate the effect of SAF-A on DNA replication. First, they show that SAF-A is required for robust DNA replication under normal conditions, as well as after replication stress in cultured cells in which SAF-A has been silenced. Next, licensing assays and DNA combing experiments suggest that SAF-A participates in different replication stages, including replication licensing, origin activation and fork progression. The authors then utilise single-cell replication timing analysis to reveal that SAF-A depletion affects replication timing domains, suggesting a role for SAF-A in defining the chromatin boundaries during genome-wide replication. Finally, they show that loss of these functions in SAF-A-depleted cells leads to replication stress and increased entry to quiescence. Taken together, these results uncover a new function of SAF-A in supporting DNA replication, and suggest an important interplay between chromatin structure and the DNA replication machinery.
