Abstract
DNA double-strand breaks are genotoxic lesions whose repair can be templated off an intact DNA duplex through the conserved homologous recombination (HR) pathway. Because it mainly consists of a succession of non-covalent associations of molecules, HR is intrinsically reversible. Reversibility serves as an integral property of HR, exploited and tuned at various stages throughout the pathway with anti- and pro-recombinogenic consequences. Here, we focus on the reversibility of displacement loops (D-loops), a central DNA joint molecule intermediate whose dynamics and regulation have recently been physically probed in somatic S. cerevisiae cells. From homology search to repair completion, we discuss putative roles of D-loop reversibility in repair fidelity and outcome.
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Acknowledgements
AP was supported by fellowships from the ARC Foundation, the EMBO (ALTF-238-2013), the Framework Project 7 of the European Union (Marie Curie International Outgoing Fellowship 628355) administered by the Institut Pasteur, France, and received financial support from the Philippe Foundation. Research in the WDH laboratory is supported by NIH grants GM58015 and CA92276.
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Glossary
- Break-induced replication (BIR):
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The long-range DNA synthesis initiated at a DSB site that involves extension of a D-loop.
- Crossover (CO) and non-crossover (NCO):
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The outcomes of HR repair that, respectively, involves or not the physical exchange of DNA strands between the broken and the donor molecule.
- D-loop (or displacement loop):
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A DNA joint molecule formed upon pairing of a single-stranded DNA to its complement present in a duplex DNA.
- Homologous recombination (HR):
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A conserved DSB repair pathway that uses an intact DNA molecule as a template for repair.
- Helicase:
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A protein that uses the energy of ATP hydrolysis to translocate directionally on single-stranded DNA and separate the two strands of duplex DNA.
- Multi-invasion-induced rearrangement (MIR):
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A tripartite recombination pathway initiated by a DSB end and that causes rearrangement of two independent donor molecules upon endonucleolytic cleavage of D-loops.
- Nucleo-protein filament (NPF):
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A helical filament formed by the oligomerization of Rad51 (in eukaryotes) and associated proteins onto the single-stranded DNA formed on each side of the break by resection.
- Structure-selective endonuclease (SSE):
-
A protein that recognizes and selectively cleaves DNA structures that are more complex than single-stranded DNA or duplex DNA (such as flaps, D-loops, Holliday junctions, and forks).
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Piazza, A., Heyer, WD. Moving forward one step back at a time: reversibility during homologous recombination. Curr Genet 65, 1333–1340 (2019). https://doi.org/10.1007/s00294-019-00995-7
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DOI: https://doi.org/10.1007/s00294-019-00995-7