Repo-man at the intersection of chromatin remodelling, DNA repair, nuclear envelope organization, and cancer progression

Abstract

Nuclear structure and chromatin changes are very useful biomarkers in cancer diagnosis. Despite this, their biological significance and relevance to cancer progression are still not well understood. The identification of new proteins that link the nuclear envelope to chromatin organization and the understanding of the molecular mechanisms underlying these connections have begun to provide some important clues. This review discusses the role of the nuclear protein Repo-Man (CDCA2) in the maintenance of genome stability. Repo-Man (CDCA2) is a targeting subunit for the protein phosphatase 1 involved in the dephosphorylation of histone H3 during mitotic exit. In this role, it is important for the chromatin organization in post-mitotic nuclei. Repo-Man (CDCA2) is also essential for proper nuclear envelope reformation and the regulation of DNA damage responses. The relevance of this complex for cancer biology is also corroborated by emerging evidence that provides a correlation between Repo-Man (CDCA2) expression levels and cancer progression; several studies now suggest that Repo-Man (CDCA2) represents a very strong prognostic marker for poor patient survival.