Oshidari Roxanne, Mekhail Karim
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.
Methods Mol Biol. 2018;1672:375-385. doi: 10.1007/978-1-4939-7306-4_26.
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.
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。
Methods Mol Biol. 2018
Cold Spring Harb Perspect Biol. 2014-9-16
DNA Repair (Amst). 2011-4-3
Nucleic Acids Res. 2015-9-18