The histone methyltransferase SUVR2 promotes DSB repair via chromatin remodeling and liquid- liquid phase separation

MOLECULAR PLANT(2022)

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摘要
Maintaining genomic integrity and stability is particularly important for stem cells, which are at the top of the cell lineage origin. Here, we discovered that the plant-specific histone methyltransferase SUVR2 main-tains the genome integrity of the root tip stem cells through chromatin remodeling and liquid???liquid phase separation (LLPS) when facing DNA double-strand breaks (DSBs). The histone methyltransferase SUVR2 (MtSUVR2) has histone methyltransferase activity and catalyzes the conversion of histone H3 lysine 9 monomethylation (H3K9me1) to H3K9me2/3 in vitro and in Medicago truncatula. Under DNA damage, the proportion of heterochromatin decreased and the level of DSB damage marker g-H2AX increased in suvr2 mutants, indicating that MtSUVR2 promotes the compaction of the chromatin structure through H3K9 methylation modification to protect DNA from damage. Interestingly, MtSUVR2 was induced by DSBs to phase separate and form droplets to localize at the damage sites, and this was confirmed by immu-nofluorescence and fluorescence recovery after photobleaching experiments. The IDR1 and low -complexity domain regions of MtSUVR2 determined its phase separation in the nucleus, whereas the IDR2 region determined the interaction with the homologous recombinase MtRAD51. Furthermore, we found that MtSUVR2 drove the phase separation of MtRAD51 to form ???DNA repair bodies,???which could enhance the stability of MtRAD51 proteins to facilitate error-free homologous recombination repair of stem cells. Taken together, our study reveals that chromatin remodeling-associated proteins participate in DNA repair through LLPS.
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stem cell,droplets,SUVR2,Medicago truncatula
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