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

Alexander J Bishop, R. H. Schiestl

Research output: Contribution to journalArticle

59 Citations (Scopus)

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

Fingerprint

Homologous Recombination
Genome
Sequence Homology
Environmental Carcinogens
Recombinational DNA Repair
Inborn Genetic Diseases
Gene Duplication
DNA Repair
Carcinogens
Introns
Genetic Recombination
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Homologous recombination as a mechanism for genome rearrangements : Environmental and genetic effects. / Bishop, Alexander J; Schiestl, R. H.

In: Human Molecular Genetics, Vol. 9, No. 16 REV. ISS., 2000, p. 2427-2434.

Research output: Contribution to journalArticle

@article{03b984f425a54861bbb5567445c226b2,
title = "Homologous recombination as a mechanism for genome rearrangements: Environmental and genetic effects",
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.",
author = "Bishop, {Alexander J} and Schiestl, {R. H.}",
year = "2000",
language = "English (US)",
volume = "9",
pages = "2427--2434",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "16 REV. ISS.",

}

TY - JOUR

T1 - Homologous recombination as a mechanism for genome rearrangements

T2 - Environmental and genetic effects

AU - Bishop, Alexander J

AU - Schiestl, R. H.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033753844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033753844&partnerID=8YFLogxK

M3 - Article

C2 - 11005798

AN - SCOPUS:0033753844

VL - 9

SP - 2427

EP - 2434

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 16 REV. ISS.

ER -