期刊
DNA REPAIR
卷 7, 期 6, 页码 983-989出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2008.02.006
关键词
LINE; genetic instability; L1; transpose; DNA damage; nucleotide excision repair; target primed reverse transcription
资金
- NCRR NIH HHS [P20 RR020152-047682, P20 RR020152] Funding Source: Medline
- NIGMS NIH HHS [R01 GM045668-15, R01 GM045668, R01 GM079709, R01 GM079709-01A1, R01GM45668] Funding Source: Medline
Retrotransposons are currently active in the human and mouse genomes contributing to novel disease mutations and genomic variation via de novo insertions. However, little is known about the interactions of non-long terminal repeat (non-LTR) retrotransposons with the host DNA repair machinery. Based on the model of retrotransposition for the human and mouse LINE-1 element, one likely intermediate is an extension of cDNA that is heterologous to the genomic target, a flap intermediate. To determine whether a human flap endonuclease could recognize and process this potential intermediate, the genetic requirement for the ERCC1/XPF heterodimer during LINE-1 retrotransposition was characterized. Reduction of XPF in human cells increased retrotransposition whereas complementation of ERCC1-deficiency in hamster cells reduced retrotransposition. These results demonstrate for the first time that DNA repair enzymes act to limit non-LTR retrotransposition and may provide insight into the genetic instability phenotypes of ercc1 and xpf individuals. (c) 2008 Elsevier B.V. All rights reserved.
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