BIOLOGY OF THE P53 PROTEIN

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The Proliferating Cell Nuclear Antigen (PCNA), as the co-factor of DNA polymerase delta, is absolutely required for DNA replication and cellular proliferation. The expression of PCNA, like the expression of other genes coding for proteins of the DNA synthesizing apparatus, increases sharply at the G1/S boundary in Go cells stimulated by serum or growth factors. The co-ordinate expression of these genes indicates that, although some diversity may be present, some common mechanism(s) must also be operative in their near-simultaneous activation. By investigating the regulation of PCNA expression, we hope to identify regulatory proteins that not only modulate PCNA expression (in itself of considerable interest) but may be also involved in the regulation of other G1/S boundary genes. Since the G1/S transition is one of the critical steps in the control of cell proliferation, the identification of regulatory proteins at this point is of major significance.