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- Title
Primary cilia and the DNA damage response: linking a cellular antenna and nuclear signals.
- Authors
Morrison, Ciaran G.
- Abstract
The maintenance of genome stability involves integrated biochemical activities that detect DNA damage or incomplete replication, delay the cell cycle, and direct DNA repair activities on the affected chromatin. These processes, collectively termed the DNA damage response (DDR), are crucial for cell survival and to avoid disease, particularly cancer. Recent work has highlighted links between the DDR and the primary cilium, an antenna-like, microtubule-based signalling structure that extends from a centriole docked at the cell surface. Ciliary dysfunction gives rise to a range of complex human developmental disorders termed the ciliopathies. Mutations in ciliopathy genes have been shown to impact on several functions that relate to centrosome integrity, DNA damage signalling, responses to problems in DNA replication and the control of gene expression. This review covers recent findings that link cilia and the DDR and explores the various roles played by key genes in these two contexts. It outlines how proteins encoded by ciliary genes impact checkpoint signalling, DNA replication and repair, gene expression and chromatin remodelling. It discusses how these diverse activities may integrate nuclear responses with those that affect a structure of the cell periphery. Additional directions for exploration of the interplay between these pathways are highlighted, with a focus on new ciliary gene candidates that alter genome stability.
- Subjects
DNA damage; CILIA &; ciliary motion; CELL survival; DNA replication; DNA repair; GENE expression
- Publication
Biochemical Society Transactions, 2021, Vol 49, Issue 2, p829
- ISSN
0300-5127
- Publication type
Article
- DOI
10.1042/BST20200751