Scientific article
Open access

Loss of histone H3.3 results in DNA replication defects and altered origin dynamics in C. elegans

Published inGenome research, vol. 30, no. 12, p. 1740-1751
Publication date2020-12-10
First online date2020-11-10

Histone H3.3 is a replication-independent variant of histone H3 with important roles in development, differentiation, and fertility. Here, we show that loss of H3.3 results in replication defects in Caenorhabditis elegans embryos at elevated temperatures. To characterize these defects, we adapt methods to determine replication timing, map replication origins, and examine replication fork progression. Our analysis of the spatiotemporal regulation of DNA replication shows that despite the very rapid embryonic cell cycle, the genome is replicated from early and late firing origins and is partitioned into domains of early and late replication. We find that under temperature stress conditions, additional replication origins become activated. Moreover, loss of H3.3 results in altered replication fork progression around origins, which is particularly evident at stress-activated origins. These replication defects are accompanied by replication checkpoint activation, a delayed cell cycle, and increased lethality in checkpoint-compromised embryos. Our comprehensive analysis of DNA replication in C. elegans reveals the genomic location of replication origins and the dynamics of their firing, and uncovers a role of H3.3 in the regulation of replication origins under stress conditions.

Citation (ISO format)
STROBINO, Maude et al. Loss of histone H3.3 results in DNA replication defects and altered origin dynamics in<i> C. elegans</i>. In: Genome research, 2020, vol. 30, n° 12, p. 1740–1751. doi: 10.1101/gr.260794.120
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Article (Published version)
ISSN of the journal1088-9051

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