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Homologous Recombination as a Fundamental Genome Surveillance Mechanism during DNA Replication
Julian Spies1, Hana Polasek-Sedlackova1, Jiri Lukas1
1Novo Nordisk Foundation Center for Protein Research, Protein Signaling Program, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark.
Genes
|December 24, 2021
Summary
Cancer cells exploit DNA replication stress responses, particularly homologous recombination (HR), to promote evolution and therapy resistance. This review details HR-mediated repair of daughter strand gaps (DSGs) and its therapeutic targeting.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Biology
Background:
- Accurate genome replication is vital for cell division and stability.
- Replication stress (RS) challenges DNA replication forks, a common feature in cancer.
- Cells employ mechanisms like homologous recombination (HR) to protect genomes during RS.
Purpose of the Study:
- To review recent insights into HR-mediated protection of replication intermediates during RS.
- To focus on the repair of daughter strand gaps (DSGs) arising from replication across damaged DNA.
- To discuss the role of DSG repair in cancer evolution and therapeutic targeting.
Main Methods:
- Literature review of recent studies on DNA replication stress and homologous recombination.
- Analysis of mechanisms underlying HR-mediated protection of DSGs.
- Examination of pathophysiological scenarios impacting DSG repair.
Main Results:
- HR plays a crucial role in protecting and repairing DSGs during replication stress.
- DSG repair mechanisms vary based on the extent and duration of RS.
- Silencing of DSG repair in certain pathophysiological states promotes mutagenesis and cancer evolution.
Conclusions:
- Cancer cells manipulate RS responses, including HR and DSG repair, for growth and therapeutic resistance.
- Understanding DSG repair offers potential therapeutic targets for cancer treatment.
- Targeting these adaptive responses could inhibit cancer evolution and overcome resistance.
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