CONTEXT

Anomalies during DNA replication process are involved in different pathologies such as brains diseases, haematological disorders and cancers. Thus, means to control cellular division would be useful tools for the treatment of pathologies linked to a dysfunction of DNA replication or for pathologies linked to an excessive cellular proliferation. The MiniChromosome Maintenance family (MCM2-8) comprises structurally related proteins required to initiate DNA synthesis in eukaryotes. These proteins function in a complex very likely as a DNA helicase in promoting the opening of the DNA double helix at replication origins. Here we report the identification of a novel member of this family, the MCM9 protein.

TECHNICAL DESCRIPTION

This invention concerns the use of the human or animal MCM9 gene, or parts of said gene, or transcripts thereof, or antisense nucleic acids able to hybridize with part of said gene or transcripts, or silencing RNA derived from parts of said transcripts. The inventors have performed the complete identification of a novel member of the MCM2-8 family represented by the members MCM2-7 and MCM8, 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, in addition, MCM9 contains a unique carboxy-terminal domain which has only weak homology to MCM2-7 and MCM8, but stretches of amino acids, ranging from4 to 10 amino acids, are highly conserved within MCM9 homologs. The inventors have also shown that the human MCM9 protein, which resembles a truncated MCM-like protein missing a part of the MCM2-7 domain, is an incomplete form of the full length human MCM9 protein. Searching the human genome with either the newly identified human MCM9 or other MCM protein sequences, the inventors have not detected 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.

INDUSTRIAL APPLICATIONS

This invention relates to the preparation of a pharmaceutical composition for the treatment of pathologies linked to a dysfunction of the expression of the MCM9 gene. – Use of the MCM9 gene in pathologies linked to a dysfunction of DNA replication or to an excessive cell proliferation like choriocarcinoma, skin melanoma, colon adenocarcinoma, etc. – Treatment of pathologies characterised by a predisposition toward cancer caused by the defect of the helicase function like Bloom’s syndrome or xeroderma pigmentosum.

Articles

Lutzmann et al., Gene 2005

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