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与起始识别复合物的关联表明组蛋白乙酰转移酶Hat1p/Hat2p具有新功能。

Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p.

作者信息

Suter Bernhard, Pogoutse Oxana, Guo Xinghua, Krogan Nevan, Lewis Peter, Greenblatt Jack F, Rine Jasper, Emili Andrew

机构信息

Program in Proteomics and Bioinformatics, Banting and Best Department of Medical Genetics, University of Toronto, Toronto, Ontario, Canada.

出版信息

BMC Biol. 2007 Sep 19;5:38. doi: 10.1186/1741-7007-5-38.

DOI:10.1186/1741-7007-5-38
PMID:17880717
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2140264/
Abstract

BACKGROUND

Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4.

RESULTS

Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC). While mutational inactivation of the histone acetyltransferase (HAT) gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2) exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork.

CONCLUSION

We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p). The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.

摘要

背景

组蛋白修饰已被证明参与转录调控，最近还发现其与DNA复制和修复有关。在酵母中，一种主要的保守组蛋白乙酰转移酶Hat1p优先使组蛋白H4上的赖氨酸残基5和12发生乙酰化。

结果

在此，我们报道由Hat1p及其伴侣Hat2p组成的核亚复合物在物理和功能上与起源识别复合物（ORC）相互作用。虽然单独的组蛋白乙酰转移酶（HAT）基因HAT1的突变失活不会损害起源激发或DNA复制的起始，但HAT1（或HAT2）的缺失会加剧条件性orc-ts突变体的生长缺陷。因此，与ORC相关的Hat1p依赖性组蛋白乙酰转移酶活性表明组蛋白修饰与DNA复制之间存在新的联系。额外的遗传和生化证据表明，除了Hat1p/Hat2p之外，还存在部分重叠的组蛋白H3乙酰转移酶活性，以确保适当的DNA复制效率。此外，我们证明了Hat1p在S期与染色质的动态关联，这表明该酶在复制叉处发挥作用。

结论

我们发现了Hat1p依赖性组蛋白乙酰转移酶一个有趣的新关联，除了其先前已知的在核染色质组装中的作用（Hat1p/Hat2p-Hif1p）。一个独特的Hat1p/Hat2p亚复合物的参与表明组蛋白H4修饰与ORC依赖性DNA复制之间存在联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/8620a0afc027/1741-7007-5-38-9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/e9e093f1f0cd/1741-7007-5-38-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/47835e14cc68/1741-7007-5-38-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/d4051405326c/1741-7007-5-38-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/c9d581c49e87/1741-7007-5-38-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/7bc2e6866030/1741-7007-5-38-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/4abfa10cf4b1/1741-7007-5-38-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/ed4802c91e2d/1741-7007-5-38-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/4670258a45a0/1741-7007-5-38-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/8620a0afc027/1741-7007-5-38-9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/e9e093f1f0cd/1741-7007-5-38-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/47835e14cc68/1741-7007-5-38-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/d4051405326c/1741-7007-5-38-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/c9d581c49e87/1741-7007-5-38-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/7bc2e6866030/1741-7007-5-38-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/4abfa10cf4b1/1741-7007-5-38-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/ed4802c91e2d/1741-7007-5-38-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/4670258a45a0/1741-7007-5-38-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e90d/2140264/8620a0afc027/1741-7007-5-38-9.jpg

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