Oct 6, 2015

Methylation of histone H4 lysine 20 by PR-Set7 ensures the integrity of late replicating sequence domains in Drosophila

BioRxiv : the Preprint Server for Biology
Yulong Li, Robin L Armstrong


The local chromatin environment is a key regulator of DNA-templated processes including transcription, DNA replication, and DNA repair. The methylation state of lysine 20 on histone H4 (H4K20) has been linked to cell cycle progression, origin recognition complex (ORC) binding, pre-Replication Complex (pre-RC) assembly, and activation of replication origins. Monomethylation of H4K20 (H4K20me1) is mediated by the cell cycle-regulated histone methyltransferase PR-Set7. PR-Set7 depletion in mammalian cells results in defective S-phase progression and the accumulation of DNA damage, which could be partially attributed to a defect in pre-RC formation and origin activity. However, these studies were limited to only a handful of mammalian origins, and it remains unclear how PR-Set7 and H4K20 methylation impact the replication program on a genomic scale. Using Drosophila Kc167 cells, we employed genetic, cytological, and genomic approaches to better understand the role of PR-Set7 and H4K20 methylation in regulating DNA replication and governing genome stability. We find that depletion of Drosophila PR-Set7 and loss of H4K20me1 result in the accumulation of DNA damage and an ATR-dependent cell cycle arrest. The cell cycle arrest occurs d...Continue Reading

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Mentioned in this Paper

Biological Markers
Cell Cycle Progression
Protein Methylation
DNA Repair
Pre-replicative Complex Assembly
SETD7 protein, human
Transcription, Genetic

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