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研究端粒处可诱导性DNA双链断裂修复的实验方法。

Assays to Study Repair of Inducible DNA Double-Strand Breaks at Telomeres.

作者信息

Oshidari Roxanne, Mekhail Karim

机构信息

Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 661 University Ave., Toronto, ON, M5G 1M1, Canada.

Canada Research Chairs Program, Faculty of Medicine, University of Toronto, 661 University Ave., Toronto, ON, M5G 1M1, Canada.

出版信息

Methods Mol Biol. 2018;1672:375-385. doi: 10.1007/978-1-4939-7306-4_26.


DOI:10.1007/978-1-4939-7306-4_26
PMID:29043637
Abstract

The ends of linear chromosomes are constituted of repetitive DNA sequences called telomeres. Telomeres, nearby regions called subtelomeres, and their associated factors prevent chromosome erosion over cycles of DNA replication and prevent chromosome ends from being recognized as DNA double-strand breaks (DSBs). This raises the question of how cells repair DSBs that actually occur near chromosome ends. One approach is to edit the genome and engineer cells harboring inducible DSB sites within the subtelomeric region of different chromosome ends. This provides a reductionist and tractable genetic model system in which mechanisms mediating repair can be dissected via genetics, molecular biology, and microscopy tools.

摘要

线性染色体的末端由称为端粒的重复DNA序列构成。端粒、称为亚端粒的附近区域及其相关因子可防止DNA复制周期中的染色体侵蚀,并防止染色体末端被识别为DNA双链断裂(DSB)。这就提出了一个问题:细胞如何修复实际发生在染色体末端附近的DSB。一种方法是编辑基因组并构建在不同染色体末端亚端粒区域内含有可诱导DSB位点的细胞。这提供了一个简化且易于处理的遗传模型系统,其中介导修复的机制可以通过遗传学、分子生物学和显微镜工具进行剖析。

相似文献

[1]
Assays to Study Repair of Inducible DNA Double-Strand Breaks at Telomeres.

Methods Mol Biol. 2018

[2]
The DNA damage response at dysfunctional telomeres, and at interstitial and subtelomeric DNA double-strand breaks.

Genes Genet Syst. 2018-1-20

[3]
NHEJ Contributes to the Fast Repair of Radiation-induced DNA Double-strand Breaks at Late Prophase I Telomeres.

Health Phys. 2018-7

[4]
Differences in the recruitment of DNA repair proteins at subtelomeric and interstitial I-SceI endonuclease-induced DNA double-strand breaks.

DNA Repair (Amst). 2017-1

[5]
Recombination at subtelomeres is regulated by physical distance, double-strand break resection and chromatin status.

EMBO J. 2017-9-1

[6]
The role of double-strand break repair pathways at functional and dysfunctional telomeres.

Cold Spring Harb Perspect Biol. 2014-9-16

[7]
Subtelomeric regions in mammalian cells are deficient in DNA double-strand break repair.

DNA Repair (Amst). 2011-4-3

[8]
The role of ATM in the deficiency in nonhomologous end-joining near telomeres in a human cancer cell line.

PLoS Genet. 2013-3-28

[9]
Asymmetric Processing of DNA Ends at a Double-Strand Break Leads to Unconstrained Dynamics and Ectopic Translocation.

Cell Rep. 2018-9-4

[10]
Processing by MRE11 is involved in the sensitivity of subtelomeric regions to DNA double-strand breaks.

Nucleic Acids Res. 2015-9-18

引用本文的文献

[1]
Nuclear microtubule filaments mediate non-linear directional motion of chromatin and promote DNA repair.

Nat Commun. 2018-7-2

[2]
Defining the Damaged DNA Mobility Paradox as Revealed by the Study of Telomeres, DSBs, Microtubules and Motors.

Front Genet. 2018-3-20

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