Genome organization influences partner selection for chromosomal rearrangements

TY - JOUR

T1 - Genome organization influences partner selection for chromosomal rearrangements

AU - Wijchers, P.J.

AU - de Laat, W.

N1 - Reporting year: 2010 Metis note: S0168-9525(10)00221-0 [pii]; Available online 7 December 2010.

PY - 2010

Y1 - 2010

N2 - Chromosomal rearrangements occur as a consequence of the erroneous repair of DNA double-stranded breaks, and often underlie disease. The recurrent detection of specific tumorigenic rearrangements suggests that there is a mechanism behind chromosomal partner selection involving the shape of the genome. With the advent of novel high-throughput approaches, detailed genome integrity and folding maps are becoming available. Integrating these data with knowledge of experimentally induced DNA recombination strongly suggests that partner choice in chromosomal rearrangement primarily follows the three-dimensional conformation of the genome. Local rearrangements are favored over distal and interchromosomal rearrangements. This is seen for neutral rearrangements, but not necessarily for rearrangements that drive oncogenesis. The recurrent detection of tumorigenic rearrangements probably reflects their exceptional capacity to confer growth advantage to the rare cells that contain them. The abundant presence of neutral rearrangements suggests that somatic genome variation is also common in healthy tissue.

AB - Chromosomal rearrangements occur as a consequence of the erroneous repair of DNA double-stranded breaks, and often underlie disease. The recurrent detection of specific tumorigenic rearrangements suggests that there is a mechanism behind chromosomal partner selection involving the shape of the genome. With the advent of novel high-throughput approaches, detailed genome integrity and folding maps are becoming available. Integrating these data with knowledge of experimentally induced DNA recombination strongly suggests that partner choice in chromosomal rearrangement primarily follows the three-dimensional conformation of the genome. Local rearrangements are favored over distal and interchromosomal rearrangements. This is seen for neutral rearrangements, but not necessarily for rearrangements that drive oncogenesis. The recurrent detection of tumorigenic rearrangements probably reflects their exceptional capacity to confer growth advantage to the rare cells that contain them. The abundant presence of neutral rearrangements suggests that somatic genome variation is also common in healthy tissue.

U2 - 10.1016/j.tig.2010.11.001

DO - 10.1016/j.tig.2010.11.001

M3 - Article

VL - 27

SP - 63

EP - 71

JO - Trends in Genetics

JF - Trends in Genetics

SN - 0168-9525

IS - 2

ER -