Homologous recombination as a mechanism for genome rearrangements: Environmental and genetic effects

A. J.R. Bishop, R. H. Schiestl

Research output: Contribution to journalReview articlepeer-review

60 Scopus citations

Abstract

Novel findings over the last 2 years have led to an increased emphasis on homologous recombination (HR) as both a pathway for DNA repair and a cause for genomic rearrangements. Indeed, environmental carcinogens increase the frequency of HR, as can be observed when two copies of a duplicated sequence recombine to delete the intervening sequences. Such HR events between dispersed homologous sequences may result in not only deletions, but also gene duplications or translocations. These types of genomic rearrangement have been observed to be the cause of several different genetic diseases, including cancer. In reflection of this, several genes have been identified that, when mutant, predispose an individual to an increased frequency of cancer. These genes have been shown to be either directly or indirectly involved in HR. In addition, HR is induced by a wide variety of carcinogens, preferentially in proliferating cells. This fits the most current models of recombination and its involvement in reinitiating stalled replication forks. Thus, 'correct' HR repair may act with high fidelity, an important issue for proliferating cells, but in the context of alternative homologous partner sequences, 'aberrant' HR can cause genomic rearrangements with dire consequences.

Original languageEnglish (US)
Pages (from-to)2427-2434
Number of pages8
JournalHuman molecular genetics
Volume9
Issue number16 REV. ISS.
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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