Coordination of DNA Synthesis and Histone Gene Expression During Normal Cell Cycle Progression and After DNA Damage

 Abstract

Chromosomal DNA replication and histone synthesis are tightly coupled during S phase of the eukaryotic cell division cycle. Recently we reported that mRNA levels of mammalian replication-dependent histones, both linker histone H1 and four core histones (H2A, H2B, H3 and H4), are coordinately down-regulated in parallel with the inhibition of DNA synthesis upon DNA damage. Moreover, we showed that ionizing radiation induces inhibition of histone gene transcription through the G1 checkpoint pathway. These results demonstrate that histone synthesis is coordinated with DNA synthesis not only under normal growth conditions but also under conditions where DNA damage may occur. Regulation of the cyclin E-Cdk2 substrate NPAT, which is essential for both histone gene expression and S phase entry, provides a mechanism coordinating histone and DNA synthesis in mammalian cells.

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693 - 695
doi
10.4161/cc.3.6.940
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Coordination of DNA Synthesis and Histone Gene Expression During Normal Cell Cycle Progression and After DNA Damage