Nucleosome structure and repair of N-methylpurines in the GAL1-10 genes of Saccharomyces cerevisiae
Nucleosome structure and repair of N-methylpurines in the GAL1-10 genes of Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m206623200
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发表时间：
2002-11-22
影响因子：
4.8
通讯作者：
Smerdon, MJ
中科院分区：
文献类型：
--
作者：
Li, SS;Smerdon, MJ
对完整酵母细胞GAL1-10基因的核小体结构和n -甲基嘌呤的修复进行了核苷酸分辨率分析，包括它们共同的上游激活序列。在基因被抑制的葡萄糖培养中，具有固定位置的核小体存在于上游激活序列附近的区域，并且随着距离该序列的增加，核小体定位的可变性急剧增加。半乳糖诱导导致整个分析区域的核小体中断，其中靠近上游激活序列的核小体最为显著。在葡萄糖培养中，在固定位置的核小体中，n -甲基嘌呤修复与核小体定位之间存在很强的相关性，其中核小体核心DNA和连接体DNA分别发生缓慢和快速修复。半乳糖诱导增强了核小体核心DNA两条链的n -甲基嘌呤修复，在明显被破坏的固定核小体中最为显著。此外，n -甲基嘌呤主要通过mag1启动的碱基切除修复途径修复，而核苷酸切除修复对这些损伤的修复作用很小。最后，n -甲基嘌呤修复受最近邻核苷酸的显著影响，其中快速和缓慢修复分别发生在嘧啶和嘌呤之间的位点。这些结果表明，核小体定位和DNA序列显著调节了完整酵母细胞中mag1启动的碱基切除修复。
Nucleosome structure and repair of N-methylpurines were analyzed at nucleotide resolution in the divergent GAL1-10 genes of intact yeast cells, encompassing their common upstream-activating sequence. In glucose cultures where genes are repressed, nucleosomes with fixed positions exist in regions adjacent to the upstream-activating sequence, and the variability of nucleosome positioning sharply increases with increasing distance from this sequence. Galactose induction causes nucleosome disruption throughout the region analyzed, with those nucleosomes close to the upstream-activating sequence being most striking. In glucose cultures, a strong correlation between N-methylpurine repair and nucleosome positioning was seen in nucleosomes with fixed positions, where slow and fast repair occurred in nucleosome core and linker DNA, respectively. Galactose induction enhanced N-methylpurine repair in both strands of nucleosome core DNA, being most dramatic in the clearly disrupted, fixed nucleosomes. Furthermore, N-methylpurines are repaired primarily by the Mag1-initiated base excision repair pathway, and nucleotide excision repair contributes little to repair of these lesions. Finally, N-methylpurine repair is significantly affected by nearest-neighbor nucleotides, where fast and slow repair occurred in sites between pyrimidines and purines, respectively. These results indicate that nucleosome positioning and DNA sequence significantly modulate Mag1-initiated base excision repair in intact yeast cells.