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非同源末端连接修复途径参与长散在核元件逆转录转座的遗传学证据。

Genetic evidence that the non-homologous end-joining repair pathway is involved in LINE retrotransposition.

作者信息

Suzuki Jun, Yamaguchi Katsumi, Kajikawa Masaki, Ichiyanagi Kenji, Adachi Noritaka, Koyama Hideki, Takeda Shunichi, Okada Norihiro

机构信息

Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.

出版信息

PLoS Genet. 2009 Apr;5(4):e1000461. doi: 10.1371/journal.pgen.1000461. Epub 2009 Apr 24.

DOI:10.1371/journal.pgen.1000461
PMID:19390601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2666801/
Abstract

Long interspersed elements (LINEs) are transposable elements that proliferate within eukaryotic genomes, having a large impact on eukaryotic genome evolution. LINEs mobilize via a process called retrotransposition. Although the role of the LINE-encoded protein(s) in retrotransposition has been extensively investigated, the participation of host-encoded factors in retrotransposition remains unclear. To address this issue, we examined retrotransposition frequencies of two structurally different LINEs--zebrafish ZfL2-2 and human L1--in knockout chicken DT40 cell lines deficient in genes involved in the non-homologous end-joining (NHEJ) repair of DNA and in human HeLa cells treated with a drug that inhibits NHEJ. Deficiencies of NHEJ proteins decreased retrotransposition frequencies of both LINEs in these cells, suggesting that NHEJ is involved in LINE retrotransposition. More precise characterization of ZfL2-2 insertions in DT40 cells permitted us to consider the possibility of dual roles for NHEJ in LINE retrotransposition, namely to ensure efficient integration of LINEs and to restrict their full-length formation.

摘要

长散在元件(LINEs)是在真核生物基因组中增殖的转座元件,对真核生物基因组进化有重大影响。LINEs通过一种称为逆转座的过程进行移动。尽管LINE编码蛋白在逆转座中的作用已得到广泛研究,但宿主编码因子在逆转座中的参与情况仍不清楚。为了解决这个问题,我们检测了两种结构不同的LINEs——斑马鱼ZfL2-2和人类L1——在参与DNA非同源末端连接(NHEJ)修复的基因缺失的敲除鸡DT40细胞系中以及在用抑制NHEJ的药物处理的人类HeLa细胞中的逆转座频率。NHEJ蛋白的缺失降低了这些细胞中两种LINEs的逆转座频率,这表明NHEJ参与了LINE的逆转座。对DT40细胞中ZfL2-2插入的更精确表征使我们能够考虑NHEJ在LINE逆转座中的双重作用的可能性,即确保LINEs的有效整合并限制其全长形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/7fcb76c92fc2/pgen.1000461.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/272ff32c50b6/pgen.1000461.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/598faf8bf235/pgen.1000461.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/4bf4d49c68f9/pgen.1000461.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/153df9ebaa88/pgen.1000461.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/7fcb76c92fc2/pgen.1000461.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/272ff32c50b6/pgen.1000461.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/598faf8bf235/pgen.1000461.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/4bf4d49c68f9/pgen.1000461.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/153df9ebaa88/pgen.1000461.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b401/2666801/7fcb76c92fc2/pgen.1000461.g005.jpg

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