Progress in understanding the biology of the human mutagen LINE-1

Hum Mutat. 2007 Jun;28(6):527-39. doi: 10.1002/humu.20486.


Long interspersed nucleotide element (LINE)-1 retrotransposon (L1) has emerged as the largest contributor to mammalian genome mass, responsible for over 35% of the human genome. Differences in the number and activity levels of L1s contribute to interindividual variation in humans, both by affecting an individual's likelihood of acquiring new L1-mediated mutations, as well as by differentially modifying gene expression. Here, we report on recent progress in understanding L1 biology, with a focus on mechanisms of L1-mediated disease. We discuss known details of L1 life cycle, including L1 structure, transcriptional regulation, and the mechanisms of translation and retrotransposition. Current views on cell type specificity, timing, and control of retrotransposition are put forth. Finally, we discuss the role of L1 as a mutagen, using the latest findings in L1 biology to illuminate molecular mechanisms of L1-mediated gene disruption.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / physiology
  • Endoribonucleases / genetics
  • Endoribonucleases / physiology
  • Gene Expression Regulation
  • Genetic Diseases, Inborn / genetics*
  • Humans
  • Long Interspersed Nucleotide Elements / genetics*
  • Mutagenesis, Insertional
  • RNA-Directed DNA Polymerase / genetics
  • RNA-Directed DNA Polymerase / physiology


  • DNA-Binding Proteins
  • L1Hs-encoded protein p40, human
  • RNA-Directed DNA Polymerase
  • Endodeoxyribonucleases
  • Endoribonucleases
  • Serratia marcescens nuclease