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bioRxiv · 10.1101/2021.03.22.436394

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

Connolly, C.·Takahashi, S.·Miura, H.·Hiratani, I.·Gilbert, N.·Donaldson, A. D.·Hiraga, S.-i.
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Abstract

The organisation of chromatin is closely intertwined with biological activities of chromosome domains, including transcription and DNA replication status. Scaffold attachment factor A (SAF-A), also known as Heteronuclear Ribonucleoprotein Protein U (HNRNPU), contributes to the formation of open chromatin structure. Here we demonstrate that SAF-A promotes the normal progression of DNA replication, and enables resumption of replication after inhibition. We report that cells depleted for SAF-A show reduced origin licensing in G1 phase, and consequently reduced origin activation frequency in S phase. Replication forks progress slowly in cells depleted for SAF-A, also contributing to reduced DNA synthesis rate. Single-cell replication timing analysis revealed that the boundaries between early- and late-replicating domains are blurred in cells depleted for SAF-A. Associated with these defects, SAF-A-depleted cells show elevated {gamma}H2A phosphorylation and tend to enter quiescence. Overall we find that SAF-A protein promotes robust DNA replication to ensure continuing cell proliferation.

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Connolly, C., Takahashi, S., Miura, H., Hiratani, I., Gilbert, N., Donaldson, A. D., Hiraga, S.-i.. 2021-03-22. SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication. https://doi.org/10.1101/2021.03.22.436394

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