Does radial nuclear organisation influence DNA damage?
Does radial nuclear organisation influence DNA damage?
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DOI：
10.1007/s10577-005-3254-9
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发表时间：
2005-01-01
影响因子：
2.6
通讯作者：
Bickmore, WA
中科院分区：
文献类型：
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作者：
Gazave, E;Gautier, P;Bickmore, WA
有人认为，核周围的染色质可以保护核内部的DNA序列免受损伤。为了验证这一假设，我们检查了氧化或UV-C诱导的DNA修复位点的核分布。我们没有发现核周围的损伤（修复）比核内部的多。事实上，与保镖假说相反，在核内部检测到的损伤过多。人类18号或19号染色体上的基因序列与黑猩猩的对应染色体之间的比较进一步支持了这一观点。位于人类细胞核中心的第19号染色体上基因的同义替换率高于位于细胞核外围的第18号染色体上基因的同义替换率。我们的结论是，人类细胞核外围的染色质不能保护更多的内部序列免受损伤和突变。我们认为，核中心序列的染色质结构或碱基组成的特征使它们更容易受到损伤。
It has been suggested that chromatin at the nuclear periphery could act to shield DNA sequences in the nuclear interior from damage. To test this hypothesis, we have examined the nuclear distribution of sites of DNA repair induced by oxidation or UV-C. We do not detect more damage (repair) at the nuclear periphery than in the nuclear interior. In fact, contrary to the bodyguard hypothesis, there is an excess of damage detected in the nuclear interior. This is further supported by sequence comparison between genes on human chromosomes 18 or 19, and their counterparts in the chimpanzee. The synonymous substitution rate for genes on chromosome 19, which is located towards the centre of the human nucleus, was higher than that for genes on chromosome 18, which is located at the nuclear periphery. We conclude that chromatin at the periphery of the human nucleus is not able to protect more internally located sequences from damage and mutation. We suggest that features of the chromatin structure, or base composition, of sequences in the nuclear centre make them more susceptible to damage.