Allele-specific analysis of DNA replication origins in mammalian cells.
Allele-specific analysis of DNA replication origins in mammalian cells.
复制标题
DOI：
10.1038/ncomms8051
复制
发表时间：
2015-05-19
影响因子：
16.6
通讯作者：
Bouhassira EE
中科院分区：
文献类型：
--
作者：
Bartholdy B;Mukhopadhyay R;Lajugie J;Aladjem MI;Bouhassira EE
人们对控制复制起点的位置和激发时间的机制知之甚少。使用基于阶段性人类基因组中的 SNP 和插入缺失分析的新型功能基因组方法，我们观察到复制异步与染色体同源物之间多个起点的起始效率的微小累积变化相关，而不是与休眠起点的激活相关。等位基因特异性测量表明 G 四链体形成序列的存在与起始效率无关。序列分析表明，起源高度富集具有极不对称G/C和A/T核苷酸分布的序列，并且几乎完全耗尽反平行三链体形成序列。因此，我们提出，尽管复制起点中形成G4的序列丰富，但核苷酸分布的不对称性增加了起点解旋和采用非B DNA结构的倾向，而不是形成G4的能力，这与起点活性直接相关。 DNA 序列有助于复制起点激发的位置和时间。通过等位基因特异性分析，作者表明复制异步与起始起始效率的微小累积变化相关，而不是与休眠起始的激活相关。
The mechanisms that control the location and timing of firing of replication origins are poorly understood. Using a novel functional genomic approach based on the analysis of SNPs and indels in phased human genomes, we observe that replication asynchrony is associated with small cumulative variations in the initiation efficiency of multiple origins between the chromosome homologues, rather than with the activation of dormant origins. Allele-specific measurements demonstrate that the presence of G-quadruplex-forming sequences does not correlate with the efficiency of initiation. Sequence analysis reveals that the origins are highly enriched in sequences with profoundly asymmetric G/C and A/T nucleotide distributions and are almost completely depleted of antiparallel triplex-forming sequences. We therefore propose that although G4-forming sequences are abundant in replication origins, an asymmetry in nucleotide distribution, which increases the propensity of origins to unwind and adopt non-B DNA structure, rather than the ability to form G4, is directly associated with origin activity. DNA sequences contribute to the location and timing of replication origin firings. Here by allele-specific analysis, the authors show that replication asynchrony is associated with small cumulative variations in the initiation efficiency of origins, rather than with the activation of dormant origins.
登录
查看更多内容
通过基于遗传，物理和人群分析分析的结合，对家庭四重奏的完全基因组进行分阶段。
影响因子：
3.7
作者：
Lajugie J;Mukhopadhyay R;Schizas M;Lailler N;Fourel N;Bouhassira EE
通讯作者：
Bouhassira EE
影响因子：
7
作者：
Cayrou, Christelle;Coulombe, Philippe;Mechali, Marcel
通讯作者：
Mechali, Marcel
DOI：
10.1073/pnas.85.21.8081
发表时间：
1988-11-01
影响因子：
11.1
作者：
EPNER, E;FORRESTER, WC;GROUDINE, M
通讯作者：
GROUDINE, M
影响因子：
10.5
作者：
Duquette, ML;Handa, P;Maizels, N
通讯作者：
Maizels, N
影响因子：
16.8
作者：
Besnard, Emilie;Babied, Amelie;Lemaitre, Jean-Marc
通讯作者：
Lemaitre, Jean-Marc