Oncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling

Abstract HMGA2 belongs to the family of the high mobility group (HMG) proteins. It binds DNA via three AT-hook domains to the minor groove of adenine-thymine (AT) rich DNA. Recently, a new function of HMGA2 as a replication fork chaperone that protects stem and cancer cells from replication fork col...

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Autores principales:	Xiaodan Zhao, Sabrina Peter, Peter Dröge, Jie Yan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c95fdace04840abae38213a8de2e2ad
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spelling	oai:doaj.org-article:9c95fdace04840abae38213a8de2e2ad2021-12-02T15:05:08ZOncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling10.1038/s41598-017-09104-52045-2322https://doaj.org/article/9c95fdace04840abae38213a8de2e2ad2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09104-5https://doaj.org/toc/2045-2322Abstract HMGA2 belongs to the family of the high mobility group (HMG) proteins. It binds DNA via three AT-hook domains to the minor groove of adenine-thymine (AT) rich DNA. Recently, a new function of HMGA2 as a replication fork chaperone that protects stem and cancer cells from replication fork collapse induced by chemotherapeutic agents was uncovered, suggesting a previously uncharacterized binding at replication forks. In this study, we examined HMGA2 binding to four DNA structures relevant to replication forks, namely ds DNA, ss DNA, forked DNA and supercoiled DNA plectonemes. We detected HMGA2 binding to supercoiled DNA at the lowest concentration and this binding mode transiently stabilizes the supercoiled plectonemes against relaxation by type I topoisomerase. Together, these findings suggest a plausible mechanism how fork regression and collapse are attenuated by HMGA2 during replication stress, i.e. through transient stabilization of positively supercoiled plectonemes in the parental duplex.Xiaodan ZhaoSabrina PeterPeter DrögeJie YanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaodan Zhao Sabrina Peter Peter Dröge Jie Yan Oncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling
description	Abstract HMGA2 belongs to the family of the high mobility group (HMG) proteins. It binds DNA via three AT-hook domains to the minor groove of adenine-thymine (AT) rich DNA. Recently, a new function of HMGA2 as a replication fork chaperone that protects stem and cancer cells from replication fork collapse induced by chemotherapeutic agents was uncovered, suggesting a previously uncharacterized binding at replication forks. In this study, we examined HMGA2 binding to four DNA structures relevant to replication forks, namely ds DNA, ss DNA, forked DNA and supercoiled DNA plectonemes. We detected HMGA2 binding to supercoiled DNA at the lowest concentration and this binding mode transiently stabilizes the supercoiled plectonemes against relaxation by type I topoisomerase. Together, these findings suggest a plausible mechanism how fork regression and collapse are attenuated by HMGA2 during replication stress, i.e. through transient stabilization of positively supercoiled plectonemes in the parental duplex.
format	article
author	Xiaodan Zhao Sabrina Peter Peter Dröge Jie Yan
author_facet	Xiaodan Zhao Sabrina Peter Peter Dröge Jie Yan
author_sort	Xiaodan Zhao
title	Oncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling
title_short	Oncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling
title_full	Oncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling
title_fullStr	Oncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling
title_full_unstemmed	Oncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling
title_sort	oncofetal hmga2 effectively curbs unconstrained (+) and (−) dna supercoiling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9c95fdace04840abae38213a8de2e2ad
work_keys_str_mv	AT xiaodanzhao oncofetalhmga2effectivelycurbsunconstrainedanddnasupercoiling AT sabrinapeter oncofetalhmga2effectivelycurbsunconstrainedanddnasupercoiling AT peterdroge oncofetalhmga2effectivelycurbsunconstrainedanddnasupercoiling AT jieyan oncofetalhmga2effectivelycurbsunconstrainedanddnasupercoiling
_version_	1718388908622872576

Oncofetal HMGA2 effectively curbs unconstrained (+) and (−) DNA supercoiling

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