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隐匿于迷雾中的高峰:哺乳动物复制起点的图景

Peaks cloaked in the mist: the landscape of mammalian replication origins.

作者信息

Hyrien Olivier

机构信息

Institut de Biologie de l'Ecole Normale Supérieure, Centre National de la Recherche Scientifique UMR8197 and Institut National de la Santé et de la Recherche Médicale U1024, 75005 Paris, France

出版信息

J Cell Biol. 2015 Jan 19;208(2):147-60. doi: 10.1083/jcb.201407004.

DOI:10.1083/jcb.201407004
PMID:25601401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4298691/
Abstract

Replication of mammalian genomes starts at sites termed replication origins, which historically have been difficult to locate as a result of large genome sizes, limited power of genetic identification schemes, and rareness and fragility of initiation intermediates. However, origins are now mapped by the thousands using microarrays and sequencing techniques. Independent studies show modest concordance, suggesting that mammalian origins can form at any DNA sequence but are suppressed by read-through transcription or that they can overlap the 5' end or even the entire gene. These results require a critical reevaluation of whether origins form at specific DNA elements and/or epigenetic signals or require no such determinants.

摘要

哺乳动物基因组的复制起始于被称为复制起点的位点,由于基因组规模庞大、遗传识别方法的能力有限以及起始中间体的稀少和脆弱性,这些位点在历史上一直难以定位。然而,现在利用微阵列和测序技术已定位了数以千计的复制起点。独立研究显示出一定程度的一致性,这表明哺乳动物的复制起点可以在任何DNA序列处形成,但会受到通读转录的抑制,或者它们可能与5'端甚至整个基因重叠。这些结果需要对复制起点是在特定DNA元件和/或表观遗传信号处形成,还是不需要此类决定因素进行批判性的重新评估。

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Chromosoma. 2015 Mar;124(1):13-26. doi: 10.1007/s00412-014-0489-2. Epub 2014 Oct 12.
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Allele-specific genome-wide profiling in human primary erythroblasts reveal replication program organization.人类原代红细胞中全基因组等位基因特异性分析揭示了复制程序的组织方式。
PLoS Genet. 2014 May 1;10(5):e1004319. doi: 10.1371/journal.pgen.1004319. eCollection 2014 May.
3
The spatiotemporal program of DNA replication is associated with specific combinations of chromatin marks in human cells.
Mol Cell. 2025 Jan 16;85(2):238-261. doi: 10.1016/j.molcel.2024.10.035.
4
The genetic landscape of origins of replication in P. falciparum.疟原虫复制起点起源的遗传景观。
Nucleic Acids Res. 2024 Jan 25;52(2):660-676. doi: 10.1093/nar/gkad1103.
5
Dimeric G-quadruplex motifs-induced NFRs determine strong replication origins in vertebrates.二聚体 G-四联体基序诱导的 NFRs 决定脊椎动物中的强复制起点。
Nat Commun. 2023 Aug 10;14(1):4843. doi: 10.1038/s41467-023-40441-4.
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Neural network and kinetic modelling of human genome replication reveal replication origin locations and strengths.神经网络和人类基因组复制的动力学模型揭示了复制原点的位置和强度。
PLoS Comput Biol. 2023 May 30;19(5):e1011138. doi: 10.1371/journal.pcbi.1011138. eCollection 2023 May.
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Detection and characterization of constitutive replication origins defined by DNA polymerase epsilon.检测和鉴定 DNA 聚合酶 ε 定义的组成型复制起点。
BMC Biol. 2023 Feb 24;21(1):41. doi: 10.1186/s12915-023-01527-z.
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Nat Protoc. 2023 Apr;18(4):1260-1295. doi: 10.1038/s41596-022-00793-5. Epub 2023 Jan 18.
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