Regulation of homologous recombination in eukaryotes

By Wolf-Dietrich Heyer, Kirk T. Ehmsen, Jie Liu. Annual Review of Genetics, 2010

1,078 citations recorded by the source corpus.

Homologous recombination is required for accurate chromosome segregation during the first meiotic division and constitutes a key repair and tolerance pathway for complex DNA damage including DNA double-stranded breaks, interstrand crosslinks, and DNA gaps. In addition, recombination and replication are inextricably linked, as recombination recovers stalled and broken replication forks enabling the evolution of larger genomes/replicons. Defects in recombination lead to genomic instability and elevated cancer predisposition, demonstrating a clear cellular need for active recombination. However, recombination can also lead to genome rearrangements. Unrestrained recombination causes undesired endpoints (translocation, deletion, inversion) and the accumulation of toxic recombination intermediates. Evidently, homologous recombination must be carefully regulated to match specific cellular needs. Here we review the mechanistic stages and proteins in recombination that are subject to regulation and suggest that recombination achieves flexibility and robustness by proceeding through meta-stable, reversible intermediates.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bf1c94e2c086f14b9c304511c57f2ca42568bad3

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Citations in the corpus

Repair Pathway Choices and Consequences at the Double-Strand Break (2015, neutral): “Although this is homology-directed repair, one copy of the repeat and the intervening sequence between the repeats are deleted in the repair product, thus resulting in loss of genetic information (Figure 1C) [5].”
CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future (2020, background): “HDR events are generally restricted to late S and G2 phases of the cell cycle, given the availability of the sister chromatid to serve as a template at these stages, whereas NHEJ predominates the G1, S, and G2 phases (81).”
Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery (2014, background): “NHEJ dominates DNA repair during G1, S and G2 phases, whereas HDR is restricted to late S and G2 phases when DNA replication is completed and sister chromatids are available to serve as repair templates (Heyer et al., 2010).”