Identification of a </= 600-kb region on human chromosome 1q42.3 inducing cellular senescence.
Identification of a </= 600-kb region on human chromosome 1q42.3 inducing cellular senescence.
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人类染色体 1q42.3 上 </= 600-kb 区域的鉴定可诱导细胞衰老。
DOI：
10.1038/sj.onc.1206143
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发表时间：
2003
期刊：
影响因子：
8
通讯作者：
Oshimura,Mitsuo
中科院分区：
文献类型：
--
作者：
Yawata,Toshio;Kamino,Hiroki;Kugoh,Hiroyuki;Katoh,Motonobu;Nomura,Nobuo;Oishi,Michio;Horikawa,Izumi;Barrett,JCarl;Oshimura,Mitsuo
通过微细胞介导的染色体转移 (MMCT) 引入人类 1 号染色体可诱导小鼠黑色素瘤 B16-F10 细胞的细胞衰老。衰老细胞仍保持端粒酶活性，这通常与人类细胞的永生生长相关，表明在该小鼠细胞系中观察到的衰老涉及端粒酶独立机制。为了将衰老诱导基因定位到特定的染色体区域，我们采用了两种实验方法：通过一系列染色体亚可转移片段（STF）的MMCT鉴定具有衰老诱导活性的最小区域，每个片段由不同的人类1号染色体衍生区域组成；以及鉴定在逃避细胞衰老的回复克隆中从转移的1号染色体上通常删除的区域。这些方法确定了活性 STF 之间共享的 2.7-3.0 Mb 衰老诱导区域和回复克隆中的 2.4-3.0 Mb 通常删除区域。这两个区域相互重叠，将负责基因定位在染色体 1q42 上 UniSTS93710 和 D1S3542 之间 450 至 600 kb 的间隔处。 3. 这项研究为克隆和表征新型衰老诱导基因提供了必要的信息和材料，该基因在不依赖于端粒酶的途径中发挥作用，该基因可能在小鼠和人类之间保守。
The introduction of a human chromosome 1 via microcell-mediated chromosome transfer (MMCT) induces the cellular senescence in mouse melanoma B16-F10 cells. The senescent cells maintained still the telomerase activity, which is frequently associated with immortal growth of human cells, suggesting that a telomerase-independent mechanism is involved in the senescence observed in this mouse cell line. To map the senescence-inducing gene to a specific chromosomal region, we took two experimental approaches: identification of a minimal region with the senescence-inducing activity via MMCT of a series of subchromosomal transferrable fragments (STFs), each consisting of a different profile of human chromosome 1-derived regions, and identification of a region commonly deleted from the transferred chromosome 1 in the revertant clones that escaped cellular senescence. These approaches identified a 2.7–3.0 Mb of senescence-inducing region shared among the active STFs and a 2.4–3.0 Mb of commonly deleted region in the revertant clones. These two regions overlapped each other to map the responsible gene at the 450 to 600-kb interval between UniSTS93710 and D1S3542 on chromosome 1q42. 3. This study provides essential information and materials for cloning and characterization of a novel senescence-inducing gene that functions in a telomerase-independent pathway, which is likely to be conserved between mice and humans.