美国耶鲁大学Yannick Jacob和加拿大渥太华大学Jean-François Couture团队合作的最新研究探明了组蛋白变体H3.1在复制过程中调节tonsoku介导的DNA修复。这一研究成果发表在2022年3月18日出版的国际学术期刊《科学》上。

研究人员发现TONSOKU(TSK/TONSL)可挽救损坏的复制叉，通过其四三肽重复结构域识别31位的丙氨酸从而与H3.1特异性相互作用。研究结果表明，在植物缺乏ATXR5/ATXR6催化的H3组蛋白27位赖氨酸单甲基化的情况下，基因组不稳定性取决于H3.1、TSK和DNA聚合酶theta (Pol θ)。 该工作揭示了复制过程中H3.1的特异性功能，和多细胞真核生物中用于调节复制后染色质成熟和TSK的常用策略，该策略依赖于组蛋白单甲基转移酶和H3.1变体的识别。

据悉，复制依赖性组蛋白H3.1的尾部与植物和动物中复制非依赖性H3.3尾部31位氨基酸不同，但尚未有对该残基功能的研究以证明H3.1在复制期间的独特和保守作用。

附：英文原文

Title: The histone H3.1 variant regulates TONSOKU-mediated DNA repair during replication

Author: Hossein Davarinejad, Yi-Chun Huang, Benoit Mermaz, Chantal LeBlanc, Axel Poulet, Geoffrey Thomson, Valentin Joly, Marcelo Muoz, Alexis Arvanitis-Vigneault, Devisree Valsakumar, Gonzalo Villarino, Alex Ross, Benjamin H. Rotstein, Emilio I. Alarcon, Joseph S. Brunzelle, Philipp Voigt, Jie Dong, Jean-Franois Couture, Yannick Jacob

Issue&Volume: 2022-03-18

Abstract: The tail of replication-dependent histone H3.1 varies from that of replication-independent H3.3 at the amino acid located at position 31 in plants and animals, but no function has been assigned to this residue to demonstrate a unique and conserved role for H3.1 during replication. We found that TONSOKU (TSK/TONSL), which rescues broken replication forks, specifically interacts with H3.1 via recognition of alanine 31 by its tetratricopeptide repeat domain. Our results indicate that genomic instability in the absence of ATXR5/ATXR6-catalyzed histone H3 lysine 27 monomethylation in plants depends on H3.1, TSK, and DNA polymerase theta (Pol θ). This work reveals an H3.1-specific function during replication and a common strategy used in multicellular eukaryotes for regulating post-replicative chromatin maturation and TSK, which relies on histone monomethyltransferases and reading of the H3.1 variant.

DOI: abm5320

Source: https://www.science.org/doi/10.1126/science.abm5320