Epigenetic regulation of DNA homologous recombination mechanism revealed

Epigenetic regulation of DNA homologous recombination mechanism revealed

Epigenetic regulation of DNA homologous recombination mechanism revealed

Bdf1 coupled H4 acetylation modification and DNA recombination repair process Photo courtesy of Wuhan University

Bdf1 coupled H4 acetylation modification and DNA recombination repair process Photo courtesy of Wuhan University

Recently, "Cutting-edge Science" published online the latest research results of Chen Xuefeng's research group, a professor from the Department of Genetics of Wuhan University's School of Life Sciences and Hubei Key Laboratory of Cell Homeostasis
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This study reveals the conserved function and mechanism of yeast bromodomain family protein Bdf1 and its human homologous protein TAF1 in promoting DNA homologous recombination repair, which is useful for comprehensively revealing histone acetylation and bromodomain family proteins in maintaining genome stability The functions and mechanisms in this are of great significance

The title of the thesis is "Yeast bromodomain protein Bdf1 and its human homologous protein TAF1 play a conservative function in promoting homologous recombination"
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In eukaryotes, DNA wraps around histone octamers to form nucleosomes, which are highly compressed to form chromatin with nucleosomes as the basic unit
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The processes of DNA transcription, replication and repair are all closely regulated by histone post-translational modification

The research team used the model organism Saccharomyces cerevisiae as a model to screen histone acetylation-related proteins and found that the bromodomain protein Bdf1 is closely related to DNA damage repair
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Knockout of the BDF1 gene causes defects in DNA end processing, checkpoint activation, and repair protein recruitment, resulting in a decrease in cell homologous recombination repair efficiency and a decrease in resistance to DNA damage drugs

In addition, the research team also found through mass spectrometry and biochemical experiments that Bdf1 interacts with the DNA repair protein RPA, and locates the region that mediates the interaction; blocking Bdf1 from binding to chromatin or disrupting its interaction with RPA will lead to homologous recombination.
The repair efficiency decreased, and the two showed epistasis effects
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However, overexpression of RPA can significantly revert the recombination defects of the above mutants
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By cooperating with Pei Huadong's research group, the research team extended the research to human cells and found that the homologous protein TAF1 of Bdf1 in human cells also has the function of promoting homologous recombination repair, and proved that this mechanism is conserved in human cells.

Related paper information: https://doi.

https://doi.
org/10.
1002/advs.
202100753