Reference: Ricke RM and Bielinsky AK (2006) A conserved Hsp10-like domain in Mcm10 is required to stabilize the catalytic subunit of DNA polymerase-alpha in budding yeast. J Biol Chem 281(27):18414-25

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Abstract


Mcm10 is a conserved eukaryotic DNA replication factor that is required for S phase progression. Recently, Mcm10 has been shown to interact physically with the DNA polymerase-alpha (pol-alpha).primase complex. We show now that Mcm10 is in a complex with pol-alpha throughout the cell cycle. In temperature-sensitive mcm10-1 mutants, depletion of Mcm10 results in degradation of the catalytic subunit of pol-alpha, Cdc17/Pol1, regardless of whether cells are in G(1), S, or G(2) phase. Importantly, Cdc17 protein levels can be restored upon overexpression of exogenous Mcm10 in mcm10-1 mutants that are grown at the nonpermissive temperature. Moreover, overexpressed Cdc17 that is normally subject to rapid degradation is stabilized by Mcm10 co-overexpression but not by co-overexpression of the B-subunit of pol-alpha, Pol12. These results are consistent with Mcm10 having a role as a nuclear chaperone for Cdc17. Mutational analysis indicates that a conserved heat-shock protein 10 (Hsp10)-like domain in Mcm10 is required to prevent the degradation of Cdc17. Substitution of a single residue in the Hsp10-like domain of endogenous Mcm10 results in a dramatic reduction of steady-state Cdc17 levels. The high degree of evolutionary conservation of this domain implies that stabilizing Cdc17 may be a conserved function of Mcm10.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Ricke RM, Bielinsky AK
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