Histone supply regulates S phase timing and cell cycle progression.
Bottom Line: We used a histone mutation of Drosophila melanogaster to show that histone supply levels, provided by a defined number of transgenic histone genes, regulate the length of S phase during the cell cycle.Lack of de novo histone supply not only extends S phase, but also causes a cell cycle arrest during G2 phase, and thus prevents cells from entering mitosis.Our results suggest a novel cell cycle surveillance mechanism that monitors nucleosome assembly without involving the DNA repair pathways and exerts its effect via suppression of CDC25 phosphatase String expression.
Affiliation: Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.Show MeSH
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Mentions: To independently address the extend of DNA damage accumulation in HisC mutant embryos, we used TUNEL assays which support that HisC mutant cells do not accumulate significant levels of DNA damage until much later in development (≥10 hr AEL) when these embryos die (Figure 4—figure supplement 2). Finally, we performed genetic tests using mutants of loki (lok), the Drosophila DNA damage checkpoint kinase chk2 (Xu et al., 2001). Homozygous lok mutants are viable and fertile. In contrast, lok, HisC double mutant embryos exhibited the HisC phenotype (Figure 4F–H). Hence, the cell cycle arrest in HisC mutant embryos is not mediated by the chk2-dependent DNA damage checkpoint pathway.
Affiliation: Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.