Identification of full genes and proteins of MCM9, a novel, vertebrate-specific member of the MCM2-8 protein family

Institute of Human Genetics, CNRS, 141, rue de la Cardonille, 34396 Montpellier Cedex 05, France.
Gene (Impact Factor: 2.14). 01/2006; 362(1):51-6. DOI: 10.1016/j.gene.2005.07.031
Source: PubMed


MCM2-7 proteins are conserved replication factors functioning as DNA helicases during DNA synthesis. MCM8 is another member of this family, which appears to be specific for higher eukaryotes, as it is absent in worms and yeast. Here we report the complete identification of a novel member of this family, the MCM9 protein. Like MCM8, MCM9 is only present in the genome of higher eukaryotes. This protein contains an MCM8-like ATP binding and hydrolysis motif implicated in helicase activity. Strikingly, MCM9 also contains a unique carboxy-terminal domain which has only weak homology to MCM2-7 and MCM8 but is conserved within MCM9 homologs. We also show that the very recently reported human MCM9 protein (HsMCM9), which resembles a truncated MCM-like protein missing a part of the MCM2-7 signature domain, is an incomplete form of the full length HsMCM9 described here. Searching the human genome with either the newly identified human MCM9 or other MCM protein sequences, we did not detect further additional members of this DNA helicase family and suggest that it is constituted of eight members, falling into two different groups, one constituted by the MCM2-7 complex and the other by MCM8 and MCM9, which are present only in higher eukaryotes.

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Available from: Domenico Maiorano
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    • "It showed 24–31% total amino acid identity with HsMCM2–MCM8 proteins and contains a unique C-terminal domain which has only weak homology to MCM2–7 and MCM8 but is conserved within MCM9 homologs.53 The phylogenetic analysis on MCM family members indicated that MCM9 was most closely related to MCM8.52 Further studies reported that HsMCM9 is expressed and required for loading the HsMCM2–7 helicase onto chromatin during pre-RC formation.53 "
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    • "The ASF1 gene is located between exons 6 and 7 of MCM9, as is the case for the mouse MCM9 gene (Figure S1E) (Hartford et al., 2011). In addition to the full length of Mcm9, a shorter isoform that terminates at the alternative exon 7 is expressed in mouse and humans (Blanton et al., 2005; Lutzmann et al., 2005; Yoshida, 2005). Therefore, we inserted selection markers that deleted exon 2, which corresponds to the N-terminal region of Mcm9 containing the Zn-finger motif (Figures S1D and S1E). "
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    • "We found that MCM family members are present in single copies in the pea aphid genome similar to other insects (Table 2). Furthermore, pea aphids and other insects retain one copy of Mcm9 while neither Drosophila nor C. elegans possess Mcm9 (Lutzmann et al., 2005). MCM proteins bind to origin of replication sites and are required for initiating DNA replication (Maiorano et al., 2006). "
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