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Triggers for genomic rearrangements: insights into genomic, cellular and environmental influences
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Triggers for genomic rearrangements: insights into genomic, cellular and environmental influences
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Journal Article
Triggers for genomic rearrangements: insights into genomic, cellular and environmental influences
2010
Overview
Key Points
Genomic rearrangements are broadly defined as DNA alterations that range from a few hundred base pairs to several megabases and they cause structural variation in the genome.
Genomic rearrangements are involved in cancers, genomic disorders caused by rearrangements passed through the germ line, as well as in the normal generation of T cell and B cell receptor diversity.
Many genomic rearrangements are nonrandom, cell type-, cell stage- and locus-specific events that are triggered by a range of cellular mechanisms and environmental cues.
Triggers for genomic rearrangements can broadly be classified into four categories: spatial proximity, cellular stress, inappropriate repair or recombination, and DNA sequence and chromatin features.
These triggers function synergistically and are not mutually exclusive. Elucidating their relative influences and how they act together is likely to be an important area for future research.
Genomic rearrangements cause human genomic disorders and are implicated in many cancers. Many rearrangements do not occur at random and this Review brings together recent findings on different influences — from nuclear organization to DNA sequence — that affect where and when rearrangements happen.
Genomic rearrangements are associated with many human genomic disorders, including cancers. It was previously thought that most genomic rearrangements formed randomly but emerging data suggest that many are nonrandom, cell type-, cell stage- and locus-specific events. Recent studies have revealed novel cellular mechanisms and environmental cues that influence genomic rearrangements. In this Review, we consider the multitude of influences on genomic rearrangements by grouping these influences into four categories: proximity of chromosomal regions in the nucleus, cellular stress, inappropriate DNA repair or recombination, and DNA sequence and chromatin features. The synergy of these triggers can poise a cell for rearrangements and here we aim to provide a conceptual framework for understanding the genesis of genomic rearrangements.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Animals
/ Antigens
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Cancer
/ Cellular signal transduction
/ Fundamental and applied biological sciences. Psychology
/ Genetics of eukaryotes. Biological and molecular evolution
/ Genome
/ Humans
/ Kinases
/ Molecular and cellular biology
/ Proteins
