A mechanism for preventing asymmetric histone segregation onto replicating DNA strands.

Yu, Chuanhe; Gan, Haiyun; Serra-Cardona, Albert; Zhang, Lin; Gan, Songlin; Sharma, Sushma; Johansson, Erik; Chabes, Andrei et al. · Science · 2018

basic_science · Level V

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Abstract

How parental histone (H3-H4)<sub>2</sub> tetramers, the primary carriers of epigenetic modifications, are transferred onto leading and lagging strands of DNA replication forks for epigenetic inheritance remains elusive. Here we show that parental (H3-H4)<sub>2</sub> tetramers are assembled into nucleosomes onto both leading and lagging strands, with a slight preference for lagging strands. The lagging-strand preference increases markedly in budding yeast cells lacking Dpb3 and Dpb4, two subunits of the leading strand DNA polymerase, Pol ε, owing to the impairment of parental (H3-H4)<sub>2</sub> transfer to leading strands. Dpb3-Dpb4 binds H3-H4 in vitro and participates in the inheritance of heterochromatin. These results indicate that different proteins facilitate the transfer of parental (H3-H4)<sub>2</sub> onto leading versus lagging strands and that Dbp3-Dpb4 plays an important role in this poorly understood process.

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