Histone synthesis by lymphocytes in G0 and G1

Peripheral blood lymphocytes are a naturally occurring population of G0 cells which can be activated in vitro to grow and divide. Upon activation with phytohemagglutinin (PHA), they enter G1 and, after a 24-h lag, begin DNA replication (S phase). Using radioisotope labeling and gel electrophoresis of acid-soluble chromatin proteins, we investigated histone synthesis in G0, G1, and S phase cultures of human and pig lymphocytes. In G0 and G1 cultures, which have less than 0.1% S phase cells, all five histones are synthesized and are incorporated into chromatin in equimolar amounts. In G0 lymphocytes histone synthesis accounts for at least 6% of nuclear protein radioactivity, and the rate of synthesis is about 2-3% of that of S phase lymphocytes. In contrast to histone synthesis by S phase cultures, G0 and G1 histone synthesis was completely resistant to treatment with hydroxyurea.