SNF2L suppresses nascent DNA gap formation to promote DNA synthesis

Nucleosome remodelers at replication forks function in the assembly and maturation of chromatin post DNA synthesis. The ISWI chromatin remodeler SNF2L (or SMARCA1) travels with replication forks but its contribution to DNA replication remains largely unknown. We find that fork elongation is curtailed when SNF2L is absent. SNF2L deficiency elevates replication stress and causes fork collapse due to remodeling activities by fork reversal Enzymes. Mechanistically, SNF2L regulates nucleosome assembly to suppress post-replicative ssDNA gap accumulation. Gap induction is not dependent on fork remodeling and PRIMPOL. Instead, gap synthesis is driven by MRE11 and EXO1 indicating susceptibility of nascent DNA to nucleolytic cleavage and resection when SNF2L is removed. Additionally, nucleosome remodeling by SNF2L protects nascent chromatin from MNase digestion and gap induction highlighting a critical role of SNF2L in chromatin assembly post DNA synthesis to maintain unperturbed replication.