Dna2 in chromosome stability and cell survival—is it all about replication forks?

Hudson, Jessica J R and Rass, Ulrich (2021) Dna2 in chromosome stability and cell survival—is it all about replication forks? International Journal of Molecular Sciences, 22 (8). a3984 1-24. ISSN 1661-6596

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Abstract

The conserved nuclease-helicase DNA2 has been linked to mitochondrial myopathy, Seckel syndrome, and cancer. Across species, the protein is indispensable for cell proliferation. On the molecular level, DNA2 has been implicated in DNA double-strand break (DSB) repair, checkpoint activation, Okazaki fragment processing (OFP), and telomere homeostasis. More recently, a critical contribution of DNA2 to the replication stress response and recovery of stalled DNA replication forks (RFs) has emerged. Here, we review the available functional and phenotypic data and propose that the major cellular defects associated with DNA2 dysfunction, and the links that exist with human disease, can be rationalized through the fundamental importance of DNA2-dependent RF recovery to genome duplication. Being a crucial player at stalled RFs, DNA2 is a promising target for anti-cancer therapy aimed at eliminating cancer cells by replication-stress overload.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 10 May 2021 08:50
Last Modified: 10 May 2021 09:00
URI: http://sro.sussex.ac.uk/id/eprint/98924

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