Homocitrate synthase connects amino acid metabolism to chromatin functions through Esa1 and DNA damage.
Homocitrate synthase connects amino acid metabolism to chromatin functions through Esa1 and DNA damage.
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DOI：
10.1101/gad.1935910
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发表时间：
2010-09
影响因子：
10.5
通讯作者：
E. Scott;L. Pillus
中科院分区：
文献类型：
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作者：
E. Scott;L. Pillus
高柠檬酸合酶（HCS）催化赖氨酸生物合成的第一步，早期的生物化学数据将其置于细胞质或线粒体中，大多数氨基酸合成发生在那里。因此，当精细的分离技术和特异性免疫试剂清楚地证明其定位于细胞核时，这是令人惊讶的。这些观察结果提出了一个问题，即HCS是否在细胞核内具有独立于赖氨酸合成的功能。我们证明了酵母中LYS20编码的HCS通过必需的MYST家族组蛋白乙酰转移酶Esa1和H2A.Z组蛋白变体与DNA损伤修复的关键过程相关联。这一发现表明，HCS具有除了氨基酸合成的作用，并且它在涉及染色质调节的核活动中起作用，这与其先前在赖氨酸生物合成中确定的作用不同。染色质连接的作用是依赖于核定位的赖氨酸20，但独立的HCS催化活性。因此，Lys20似乎已经进化为连接细胞代谢与染色质功能的双功能蛋白。
The enzyme homocitrate synthase (HCS) catalyzes the first step in lysine biosynthesis, and early biochemical data placed it in the cytoplasm or mitochondria, where most amino acid synthesis occurs. It was therefore surprising when refined fractionation techniques and specific immunoreagents clearly demonstrated its localization to the nucleus. These observations raised the question of whether HCS had a function within the nucleus independent of lysine synthesis. We demonstrate that HCS encoded by LYS20 in yeast is linked to the key process of DNA damage repair through the essential MYST family histone acetyltransferase Esa1 and the H2A.Z histone variant. This discovery indicates that HCS has a role in addition to amino acid synthesis, and that it functions in nuclear activities involving chromatin regulation that are distinct from its previously established role in lysine biosynthesis. The chromatin-linked roles are dependent on nuclear localization of Lys20, but are independent of HCS catalytic activity. Thus, Lys20 appears to have evolved as a bifunctional protein that connects cellular metabolism with chromatin functions.