期刊
GENETICS
卷 205, 期 1, 页码 139-+出版社
GENETICS SOCIETY AMERICA
DOI: 10.1534/genetics.116.188680
关键词
L1 retrotransposon; nucleotide excision repair; target-primed reverse transcription; DNA damage; genome stability
资金
- National Institutes of Health (NIH) [P20 P20GM103518/P20RR020152, R01GM079709A, R01GM45668]
- Experimental Program to Stimulate Competitive Research/Board of Reagents Support Fund grant
- NIH/National Institute on Aging grant [5K01AG030074]
- Ellison Medical Foundation New Scholar in Aging award [AG-NS-0447-08]
- Kay Yow foundation
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR020152] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103518, R01GM045668, R01GM079709] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [K01AG030074] Funding Source: NIH RePORTER
Long interspersed elements 1 (L1) are active mobile elements that constitute almost 17% of the human genome. They amplify through a copy-and-paste mechanism termed retrotransposition, and de novo insertions related to these elements have been reported to cause 0.2% of genetic diseases. Our previous data demonstrated that the endonuclease complex ERCC1-XPF, which cleaves a 3 DNA flap structure, limits L1 retrotransposition. Although the ERCC1-XPF endonuclease participates in several different DNA repair pathways, such as single-strand annealing, or in telomere maintenance, its recruitment to DNA lesions is best characterized in the nucleotide excision repair (NER) pathway. To determine if the NER pathway prevents the insertion of retroelements in the genome, we monitored the retrotransposition efficiencies of engineered L1 elements in NER-deficient cells and in their complemented versions. Core proteins of the NER pathway, XPD and XPA, and the lesion binding protein, XPC, are involved in limiting L1 retrotransposition. In addition, sequence analysis of recovered de novo L1 inserts and their genomic locations in NER-deficient cells demonstrated the presence of abnormally large duplications at the site of insertion, suggesting that NER proteins may also play a role in the normal L1 insertion process. Here, we propose new functions for the NER pathway in the maintenance of genome integrity: limitation of insertional mutations caused by retrotransposons and the prevention of potentially mutagenic large genomic duplications at the site of retrotransposon insertion events.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据