Non-B-Form DNA Is Enriched at Centromeres.

Non-B-Form DNA Is Enriched at Centromeres.
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DOI:
10.1093/molbev/msy010
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发表时间:
2018-04-01
影响因子:
10.7
通讯作者:
Henikoff S
Henikoff S
中科院分区:
生物学1区
文献类型:
--
作者:
Kasinathan S;Henikoff S

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动物和植物的着丝粒嵌入在重复的“卫星”DNA中,但被认为是表观遗传学指定的。为了确定着丝粒的遗传特征,我们调查了来自不同真核生物的卫星DNA,并确定了预测采用非B型构象的<10 bp二分体对称性的变化。缺乏着丝粒二分体对称性的生物具有序列特异性DNA结合蛋白的结合位点,具有DNA弯曲活性。例如,人类和小鼠的着丝粒缺乏二分体对称性,但富含非B型DNA,并与保守的DNA结合蛋白CENP-B的结合位点相关,CENP-B是人工着丝粒功能所需的,但矛盾的是不是必需的。我们还检测到二分体对称性和预测的非B型DNA结构在neocentromeres,形成在异位位点。我们提出,着丝粒的形式在非B型DNA,因为二分体对称性或加强序列特异性DNA结合蛋白。这可能解决CENP-B悖论,并提供了一个通用的基础着丝粒规范。
Animal and plant centromeres are embedded in repetitive “satellite” DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA-binding proteins with DNA-bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B-form DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically nonessential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-B-form DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins. This may resolve the CENP-B paradox and provide a general basis for centromere specification.
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