Cargando…
Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles
Breakage-fusion-bridge (BFB) cycle is a series of chromosome breaks and duplications that could lead to the increased copy number of a genomic segment (gene amplification). A critical step of BFB cycles leading to gene amplification is a palindromic fusion of sister chromatids following the rupture...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834830/ https://www.ncbi.nlm.nih.gov/pubmed/23975201 http://dx.doi.org/10.1093/nar/gkt762 |
_version_ | 1782292052063551488 |
---|---|
author | Marotta, Michael Chen, Xiongfong Watanabe, Takaaki Faber, Pieter W. Diede, Scott J. Tapscott, Stephen Tubbs, Raymond Kondratova, Anna Stephens, Robert Tanaka, Hisashi |
author_facet | Marotta, Michael Chen, Xiongfong Watanabe, Takaaki Faber, Pieter W. Diede, Scott J. Tapscott, Stephen Tubbs, Raymond Kondratova, Anna Stephens, Robert Tanaka, Hisashi |
author_sort | Marotta, Michael |
collection | PubMed |
description | Breakage-fusion-bridge (BFB) cycle is a series of chromosome breaks and duplications that could lead to the increased copy number of a genomic segment (gene amplification). A critical step of BFB cycles leading to gene amplification is a palindromic fusion of sister chromatids following the rupture of a dicentric chromosome during mitosis. It is currently unknown how sister chromatid fusion is produced from a mitotic break. To delineate the process, we took an integrated genomic, cytogenetic and molecular approach for the recurrent MCL1 amplicon at chromosome 1 in human tumor cells. A newly developed next-generation sequencing-based approach identified a cluster of palindromic fusions within the amplicon at ∼50-kb intervals, indicating a series of breaks and fusions by BFB cycles. The physical location of the amplicon (at the end of a broken chromosome) further indicated BFB cycles as underlying processes. Three palindromic fusions were mediated by the homologies between two nearby inverted Alu repeats, whereas the other two fusions exhibited microhomology-mediated events. Such breakpoint sequences indicate that homology-mediated fold-back capping of broken ends followed by DNA replication is an underlying mechanism of sister chromatid fusion. Our results elucidate nucleotide-level events during BFB cycles and end processing for naturally occurring mitotic breaks. |
format | Online Article Text |
id | pubmed-3834830 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38348302013-11-21 Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles Marotta, Michael Chen, Xiongfong Watanabe, Takaaki Faber, Pieter W. Diede, Scott J. Tapscott, Stephen Tubbs, Raymond Kondratova, Anna Stephens, Robert Tanaka, Hisashi Nucleic Acids Res Genome Integrity, Repair and Replication Breakage-fusion-bridge (BFB) cycle is a series of chromosome breaks and duplications that could lead to the increased copy number of a genomic segment (gene amplification). A critical step of BFB cycles leading to gene amplification is a palindromic fusion of sister chromatids following the rupture of a dicentric chromosome during mitosis. It is currently unknown how sister chromatid fusion is produced from a mitotic break. To delineate the process, we took an integrated genomic, cytogenetic and molecular approach for the recurrent MCL1 amplicon at chromosome 1 in human tumor cells. A newly developed next-generation sequencing-based approach identified a cluster of palindromic fusions within the amplicon at ∼50-kb intervals, indicating a series of breaks and fusions by BFB cycles. The physical location of the amplicon (at the end of a broken chromosome) further indicated BFB cycles as underlying processes. Three palindromic fusions were mediated by the homologies between two nearby inverted Alu repeats, whereas the other two fusions exhibited microhomology-mediated events. Such breakpoint sequences indicate that homology-mediated fold-back capping of broken ends followed by DNA replication is an underlying mechanism of sister chromatid fusion. Our results elucidate nucleotide-level events during BFB cycles and end processing for naturally occurring mitotic breaks. Oxford University Press 2013-11 2013-08-23 /pmc/articles/PMC3834830/ /pubmed/23975201 http://dx.doi.org/10.1093/nar/gkt762 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Genome Integrity, Repair and Replication Marotta, Michael Chen, Xiongfong Watanabe, Takaaki Faber, Pieter W. Diede, Scott J. Tapscott, Stephen Tubbs, Raymond Kondratova, Anna Stephens, Robert Tanaka, Hisashi Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles |
title | Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles |
title_full | Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles |
title_fullStr | Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles |
title_full_unstemmed | Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles |
title_short | Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles |
title_sort | homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834830/ https://www.ncbi.nlm.nih.gov/pubmed/23975201 http://dx.doi.org/10.1093/nar/gkt762 |
work_keys_str_mv | AT marottamichael homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT chenxiongfong homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT watanabetakaaki homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT faberpieterw homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT diedescottj homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT tapscottstephen homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT tubbsraymond homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT kondratovaanna homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT stephensrobert homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles AT tanakahisashi homologymediatedendcappingasaprimarystepofsisterchromatidfusioninthebreakagefusionbridgecycles |