PMC:1140370 / 2198-3663 JSONTXT

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    craft-sa-dev

    All the six Mcm 27 proteins contain highly conserved DNA-dependent ATPase motifs in their central regions (15,16). Among the several stable subcomplexes which MCM proteins can generate, only the Mcm4/6/7 complex has been shown to possess an intrinsic DNA helicase activity (1014,1718). While Mcm4, Mcm6 and Mcm7 proteins make distinct contribution to its helicase activity (1113), Mcm2 or Mcm3/5 inhibit the helicase activity of the Mcm4/6/7 complex by converting its double trimer structure into a heterotetramer or heteropentamer, respectively (3,11). Chromatin immunoprecipitation assays and genetic characterization in Saccharomyces cerevisiae strongly suggested that Mcm is involved not only in initiation but also in the DNA chain elongation stage as a replicative helicase (19,20). Consistent with this notion, the processivity of the Schizosaccharomyces pombe and mouse Mcm4/6/7 complexes is significantly stimulated on forked DNA structures and it can unwind duplex DNA of 400500 bp (13,14). Mcm4/6/7 binds to fork and bubble structures in an ATP-dependent manner, and generates a double-hexameric complex, as was shown for T-antigen (13,14,21). Recently, we reported that the helicase and ATP hydrolysis activities of mammalian Mcm4/6/7 are specifically activated by single-stranded DNA containing stretches of thymine residues and proposed a novel model that Mcm may play a crucial role in selection of replication origins in higher eukaryotes (13).

    craft-ca-core-ex-dev

    All the six Mcm 27 proteins contain highly conserved DNA-dependent ATPase motifs in their central regions (15,16). Among the several stable subcomplexes which MCM proteins can generate, only the Mcm4/6/7 complex has been shown to possess an intrinsic DNA helicase activity (10–14,17–18). While Mcm4, Mcm6 and Mcm7 proteins make distinct contribution to its helicase activity (11–13), Mcm2 or Mcm3/5 inhibit the helicase activity of the Mcm4/6/7 complex by converting its double trimer structure into a heterotetramer or heteropentamer, respectively (3,11). Chromatin immunoprecipitation assays and genetic characterization in Saccharomyces cerevisiae strongly suggested that Mcm is involved not only in initiation but also in the DNA chain elongation stage as a replicative helicase (19,20). Consistent with this notion, the processivity of the Schizosaccharomyces pombe and mouse Mcm4/6/7 complexes is significantly stimulated on forked DNA structures and it can unwind duplex DNA of 400–500 bp (13,14). Mcm4/6/7 binds to fork and bubble structures in an ATP-dependent manner, and generates a double-hexameric complex, as was shown for T-antigen (13,14,21). Recently, we reported that the helicase and ATP hydrolysis activities of mammalian Mcm4/6/7 are specifically activated by single-stranded DNA containing stretches of thymine residues and proposed a novel model that Mcm may play a crucial role in selection of replication origins in higher eukaryotes (13).

    craft-ca-core-dev

    All the six Mcm 27 proteins contain highly conserved DNA-dependent ATPase motifs in their central regions (15,16). Among the several stable subcomplexes which MCM proteins can generate, only the Mcm4/6/7 complex has been shown to possess an intrinsic DNA helicase activity (10–14,17–18). While Mcm4, Mcm6 and Mcm7 proteins make distinct contribution to its helicase activity (11–13), Mcm2 or Mcm3/5 inhibit the helicase activity of the Mcm4/6/7 complex by converting its double trimer structure into a heterotetramer or heteropentamer, respectively (3,11). Chromatin immunoprecipitation assays and genetic characterization in Saccharomyces cerevisiae strongly suggested that Mcm is involved not only in initiation but also in the DNA chain elongation stage as a replicative helicase (19,20). Consistent with this notion, the processivity of the Schizosaccharomyces pombe and mouse Mcm4/6/7 complexes is significantly stimulated on forked DNA structures and it can unwind duplex DNA of 400–500 bp (13,14). Mcm4/6/7 binds to fork and bubble structures in an ATP-dependent manner, and generates a double-hexameric complex, as was shown for T-antigen (13,14,21). Recently, we reported that the helicase and ATP hydrolysis activities of mammalian Mcm4/6/7 are specifically activated by single-stranded DNA containing stretches of thymine residues and proposed a novel model that Mcm may play a crucial role in selection of replication origins in higher eukaryotes (13).

    2_test

    All the six Mcm 2–7 proteins contain highly conserved DNA-dependent ATPase motifs in their central regions (15,16). Among the several stable subcomplexes which MCM proteins can generate, only the Mcm4/6/7 complex has been shown to possess an intrinsic DNA helicase activity (10–14,17–18). While Mcm4, Mcm6 and Mcm7 proteins make distinct contribution to its helicase activity (11–13), Mcm2 or Mcm3/5 inhibit the helicase activity of the Mcm4/6/7 complex by converting its double trimer structure into a heterotetramer or heteropentamer, respectively (3,11). Chromatin immunoprecipitation assays and genetic characterization in Saccharomyces cerevisiae strongly suggested that Mcm is involved not only in initiation but also in the DNA chain elongation stage as a replicative helicase (19,20). Consistent with this notion, the processivity of the Schizosaccharomyces pombe and mouse Mcm4/6/7 complexes is significantly stimulated on forked DNA structures and it can unwind duplex DNA of 400–500 bp (13,14). Mcm4/6/7 binds to fork and bubble structures in an ATP-dependent manner, and generates a double-hexameric complex, as was shown for T-antigen (13,14,21). Recently, we reported that the helicase and ATP hydrolysis activities of mammalian Mcm4/6/7 are specifically activated by single-stranded DNA containing stretches of thymine residues and proposed a novel model that Mcm may play a crucial role in selection of replication origins in higher eukaryotes (13).