Τίτλος:
Exploring and exploiting the systemic effects of deregulated replication licensing
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Maintenance and accurate propagation of the genetic material are key features for physiological development and wellbeing. The replication licensing machinery is crucial for replication precision as it ensures that replication takes place once per cell cycle. Thus, the expression status of the components comprising the replication licensing apparatus is tightly regulated to avoid re-replication; a form of replication stress that leads to genomic instability, a hallmark of cancer. In the present review we discuss the mechanistic basis of replication licensing deregulation, which leads to systemic effects, exemplified by its role in carcinogenesis and a variety of genetic syndromes. In addition, new insights demonstrate that above a particular threshold, the replication licensing factor Cdc6 acts as global transcriptional regulator, outlining new lines of exploration. The role of the putative replication licensing factor ChlR1/DDX11, mutated in the Warsaw Breakage Syndrome, in cancer is also considered. Finally, future perspectives focused on the potential therapeutic advantage by targeting replication licensing factors, and particularly Cdc6, are discussed. © 2015 Elsevier Ltd.
Συγγραφείς:
Petrakis, T.G.
Komseli, E.-S.
Papaioannou, M.
Vougas, K.
Polyzos, A.
Myrianthopoulos, V.
Mikros, E.
Trougakos, I.P.
Thanos, D.
Branzei, D.
Townsend, P.
Gorgoulis, V.G.
Περιοδικό:
Seminars in Cancer Biology
Εκδότης:
INSTAP Academic Press
Λέξεις-κλειδιά:
cell cycle protein 6; cyclin E; Myc protein; replication factor A; replication licensing factor; transcription factor; transcription factor CTCF; transcription factor E2F; unclassified drug; uvomorulin, 3' untranslated region; binding site; cancer growth; carcinogenesis; DNA replication; epithelial mesenchymal transition; exon; gene expression regulation; gene mutation; genetic disorder; genetic transcription; genomic instability; human; malignant neoplastic disease; Meier Gorlin syndrome; nonhuman; replication licensing; Review; transcription regulation; transcriptional reprogramming; Warsaw Breakage syndrome; genetics; neoplasm, DNA Replication; Gene Expression Regulation; Genomic Instability; Humans; Neoplasms
DOI:
10.1016/j.semcancer.2015.12.002
