"Mismatch Repair proteins are recruited to replicating DNA through
interaction with Proliferating Cell Nuclear Antigen (PCNA)."
Masih PJ, Kunnev D, Melendy T
Mismatch Repair (MMR) is closely linked to DNA replication; however, other
than the role of the replicative sliding clamp (PCNA) in various MMR
functions, the linkage between DNA replication and MMR has been difficult
to investigate. Here we use an in vitro DNA replication system based on
simian virus 40, to investigate MMR recruitment to replicating DNA. Both
DNA replication and MMR proteins are recruited to replicating DNA in an
origin-dependent fashion. Primer synthesis is required for recruitment of
both PCNA and MMR proteins, but not for recruitment of the single-stranded
DNA-binding protein (RPA). Blocking PCNA recruitment to replicating DNA
with a p21-based polypeptide blocks PCNA and MMR, but not RPA recruitment.
Once PCNA and subsequent proteins required for replication are loaded onto
DNA, addition of p21 leaves PCNA on the replicating DNA, but actively
displaces MMR proteins. These findings indicate that the MMR machinery is
recruited to replicating DNA through its interaction with PCNA, and
suggests that this occurs via binding of the MMR proteins to the
multi-protein interaction sites on PCNA. These studies demonstrate the
utility of this system for further investigation of the role of DNA
replication in MMR.
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Last modification of this entry: Dec. 14, 2009
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