期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/ijms22083984
关键词
DNA replication stress; chromosome stability; stalled replication fork; replication fork reversal; chicken-foot structure; replication fork recovery; chromosome underreplication; anaphase bridge; DNA end-resection; Okazaki fragment processing
资金
- UK Government's Department of Business, Energy, and Industrial Strategy through Academy of Medical Sciences Professorship Award [AMSPR1 n1018]
DNA2, a conserved nuclease-helicase, is crucial for cell proliferation and is implicated in DNA repair, checkpoint activation, and telomere homeostasis. Its critical role in replication stress response and recovery of stalled RFs makes it a promising target for anti-cancer therapy aimed at eliminating cancer cells by replication-stress overload.
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.
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