TI  - The <prot>p21</prot> inhibitor of cyclin-dependent kinases controls DNA replication by
      interaction with <prot>PCNA</prot>.
PG  - 574-8
AB  - The <prot>p53</prot> tumour-suppressor protein controls the expression of a gene
      encoding the <prot>p21</prot> cyclin-dependent protein kinase (CDK) regulator. Levels
      of <prot>p21</prot> protein are increased in senescent cells and <prot>p21</prot> overexpression
      blocks the growth of tumour cells. In normal human cells, but not in many
      tumour cells,  <prot>p21</prot>  exists in a quaternary complex with a  cyclin , a  CDK , and
      the  <prot>proliferating-cell nuclear antigen</prot> (<prot>PCNA</prot>) .  <prot>p21</prot>  controls  CDK  activity,
      thereby affecting cell-cycle control, whereas <prot>PCNA</prot> functions in both DNA
      replication and repair. Here we use simian virus 40 DNA replication in
      vitro to show than <prot>p21</prot> directly inhibits <prot>PCNA</prot>-dependent DNA replication in
      the absence of a cyclin/CDK. Furthermore,  <prot>p21</prot>  blocks the ability of  <prot>PCNA</prot> 
      to activate <prot>DNA polymerase delta</prot>, the principal replicative DNA
      polymerase. This regulation results from a direct interaction between  <prot>p21</prot> 
      and  <prot>PCNA</prot> . Thus, during <prot>p53</prot>-mediated suppression of cell proliferation, <prot>p21</prot>
      and <prot>PCNA</prot> may be important for coordinating cell-cycle progression, DNA
      replication and repair of damaged DNA.
AD  - Cold Spring Harbor Laboratory, New York 11724.
