ijms-22-03984(1).pdf (1.66 MB)
Dna2 in chromosome stability and cell survival—is it all about replication forks?
journal contribution
posted on 2023-06-09, 23:48 authored by Jessica HudsonJessica Hudson, Ulrich RassUlrich RassThe 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.
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Publication status
- Published
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- Published version
Journal
International Journal of Molecular SciencesISSN
1661-6596Publisher
MDPIExternal DOI
Issue
8Volume
22Page range
1-24Article number
a3984Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-05-10First Open Access (FOA) Date
2021-05-10First Compliant Deposit (FCD) Date
2021-05-07Usage metrics
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