Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage

The long-standing question in radiation and cancer biology is how principles of chromosome organization impact the formation of chromosomal aberrations (CAs). To address this issue, we developed a physical modeling approach and analyzed high-throughput genomic data from chromosome conformation captu...

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Autores principales:	Yuri Eidelman, Ilya Salnikov, Svetlana Slanina, Sergey Andreev
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	chromosomal aberrations Hi-C HTGTS polymer modeling 3D chromosome organization contact-first mechanism Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d18c70af29cf4e6197314fd6532b8ef2
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spelling	oai:doaj.org-article:d18c70af29cf4e6197314fd6532b8ef22021-11-25T17:54:06ZChromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage10.3390/ijms2222121861422-00671661-6596https://doaj.org/article/d18c70af29cf4e6197314fd6532b8ef22021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12186https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The long-standing question in radiation and cancer biology is how principles of chromosome organization impact the formation of chromosomal aberrations (CAs). To address this issue, we developed a physical modeling approach and analyzed high-throughput genomic data from chromosome conformation capture (Hi-C) and translocation sequencing (HTGTS) methods. Combining modeling of chromosome structure and of chromosomal aberrations induced by ionizing radiation (IR) and nuclease we made predictions which quantitatively correlated with key experimental findings in mouse chromosomes: chromosome contact maps, high frequency of cis-translocation breakpoints far outside of the site of nuclease-induced DNA double-strand breaks (DSBs), the distinct shape of breakpoint distribution in chromosomes with different 3D organizations. These correlations support the heteropolymer globule principle of chromosome organization in G1-arrested pro-B mouse cells. The joint analysis of Hi-C, HTGTS and physical modeling data offers mechanistic insight into how chromosome structure heterogeneity, globular folding and lesion dynamics drive IR-recurrent CAs. The results provide the biophysical and computational basis for the analysis of chromosome aberration landscape under IR and nuclease-induced DSBs.Yuri EidelmanIlya SalnikovSvetlana SlaninaSergey AndreevMDPI AGarticlechromosomal aberrationsHi-CHTGTSpolymer modeling3D chromosome organizationcontact-first mechanismBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12186, p 12186 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chromosomal aberrations Hi-C HTGTS polymer modeling 3D chromosome organization contact-first mechanism Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	chromosomal aberrations Hi-C HTGTS polymer modeling 3D chromosome organization contact-first mechanism Biology (General) QH301-705.5 Chemistry QD1-999 Yuri Eidelman Ilya Salnikov Svetlana Slanina Sergey Andreev Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage
description	The long-standing question in radiation and cancer biology is how principles of chromosome organization impact the formation of chromosomal aberrations (CAs). To address this issue, we developed a physical modeling approach and analyzed high-throughput genomic data from chromosome conformation capture (Hi-C) and translocation sequencing (HTGTS) methods. Combining modeling of chromosome structure and of chromosomal aberrations induced by ionizing radiation (IR) and nuclease we made predictions which quantitatively correlated with key experimental findings in mouse chromosomes: chromosome contact maps, high frequency of cis-translocation breakpoints far outside of the site of nuclease-induced DNA double-strand breaks (DSBs), the distinct shape of breakpoint distribution in chromosomes with different 3D organizations. These correlations support the heteropolymer globule principle of chromosome organization in G1-arrested pro-B mouse cells. The joint analysis of Hi-C, HTGTS and physical modeling data offers mechanistic insight into how chromosome structure heterogeneity, globular folding and lesion dynamics drive IR-recurrent CAs. The results provide the biophysical and computational basis for the analysis of chromosome aberration landscape under IR and nuclease-induced DSBs.
format	article
author	Yuri Eidelman Ilya Salnikov Svetlana Slanina Sergey Andreev
author_facet	Yuri Eidelman Ilya Salnikov Svetlana Slanina Sergey Andreev
author_sort	Yuri Eidelman
title	Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage
title_short	Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage
title_full	Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage
title_fullStr	Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage
title_full_unstemmed	Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage
title_sort	chromosome folding promotes intrachromosomal aberrations under radiation- and nuclease-induced dna breakage
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d18c70af29cf4e6197314fd6532b8ef2
work_keys_str_mv	AT yurieidelman chromosomefoldingpromotesintrachromosomalaberrationsunderradiationandnucleaseinduceddnabreakage AT ilyasalnikov chromosomefoldingpromotesintrachromosomalaberrationsunderradiationandnucleaseinduceddnabreakage AT svetlanaslanina chromosomefoldingpromotesintrachromosomalaberrationsunderradiationandnucleaseinduceddnabreakage AT sergeyandreev chromosomefoldingpromotesintrachromosomalaberrationsunderradiationandnucleaseinduceddnabreakage
_version_	1718411889055105024

Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage

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