Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination

Genes & Development
Justin B SteinfeldEric C Greene

Abstract

The vast majority of eukaryotes possess two DNA recombinases: Rad51, which is ubiquitously expressed, and Dmc1, which is meiosis-specific. The evolutionary origins of this two-recombinase system remain poorly understood. Interestingly, Dmc1 can stabilize mismatch-containing base triplets, whereas Rad51 cannot. Here, we demonstrate that this difference can be attributed to three amino acids conserved only within the Dmc1 lineage of the Rad51/RecA family. Chimeric Rad51 mutants harboring Dmc1-specific amino acids gain the ability to stabilize heteroduplex DNA joints with mismatch-containing base triplets, whereas Dmc1 mutants with Rad51-specific amino acids lose this ability. Remarkably, RAD-51 from Caenorhabditis elegans, an organism without Dmc1, has acquired "Dmc1-like" amino acids. Chimeric C. elegans RAD-51 harboring "canonical" Rad51 amino acids gives rise to toxic recombination intermediates, which must be actively dismantled to permit normal meiotic progression. We propose that Dmc1 lineage-specific amino acids involved in the stabilization of heteroduplex DNA joints with mismatch-containing base triplets may contribute to normal meiotic recombination.

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Citations

May 15, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wei-Hsuan LanHung-Wen Li
Jul 12, 2020·Yeast·Christopher M FurmanEric Alani
Jul 15, 2020·Annual Review of Genetics·Braulio BonillaKara A Bernstein
Feb 18, 2021·Proceedings of the National Academy of Sciences of the United States of America·Wan-Chen LiTing-Fang Wang
May 5, 2020·Molecular Cell·Shaun E PetersonMaria Jasin
May 18, 2021·Frontiers in Cell and Developmental Biology·Qianyan Li, JoAnne Engebrecht
Jun 30, 2021·Current Opinion in Genetics & Development·Ondrej BelanSimon J Boulton
Aug 28, 2021·Genes·Hang Phuong LeJie Liu

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