Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.

Large numbers of gross chromosomal rearrangements (GCRs) are frequently observed in many cancers. High mobility group 1 (HMG1) protein is a non-histone DNA-binding protein and is highly expressed in different types of tumors. The high expression of HMG1 could alter DNA structure resulting in GCRs. S...

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Autores principales:	Nilabja Sikdar, Soma Banerjee, Han Zhang, Stephanie Smith, Kyungjae Myung
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/42073c20706446bf85e29322de1ba02f
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spelling	oai:doaj.org-article:42073c20706446bf85e29322de1ba02f2021-11-25T05:52:54ZSpt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.1553-73901553-740410.1371/journal.pgen.1000290https://doaj.org/article/42073c20706446bf85e29322de1ba02f2008-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19057669/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Large numbers of gross chromosomal rearrangements (GCRs) are frequently observed in many cancers. High mobility group 1 (HMG1) protein is a non-histone DNA-binding protein and is highly expressed in different types of tumors. The high expression of HMG1 could alter DNA structure resulting in GCRs. Spt2p is a non-histone DNA binding protein in Saccharomyces cerevisiae and shares homology with mammalian HMG1 protein. We found that Spt2p overexpression enhances GCRs dependent on proteins for transcription elongation and polyadenylation. Excess Spt2p increases the number of cells in S phase and the amount of single-stranded DNA (ssDNA) that might be susceptible to cause DNA damage and GCR. Consistently, RNase H expression, which reduces levels of ssDNA, decreased GCRs in cells expressing high level of Spt2p. Lastly, high transcription in the chromosome V, the location at which GCR is monitored, also enhanced GCR formation. We propose a new pathway for GCR where DNA intermediates formed during transcription can lead to genomic instability.Nilabja SikdarSoma BanerjeeHan ZhangStephanie SmithKyungjae MyungPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 4, Iss 12, p e1000290 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Nilabja Sikdar Soma Banerjee Han Zhang Stephanie Smith Kyungjae Myung Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.
description	Large numbers of gross chromosomal rearrangements (GCRs) are frequently observed in many cancers. High mobility group 1 (HMG1) protein is a non-histone DNA-binding protein and is highly expressed in different types of tumors. The high expression of HMG1 could alter DNA structure resulting in GCRs. Spt2p is a non-histone DNA binding protein in Saccharomyces cerevisiae and shares homology with mammalian HMG1 protein. We found that Spt2p overexpression enhances GCRs dependent on proteins for transcription elongation and polyadenylation. Excess Spt2p increases the number of cells in S phase and the amount of single-stranded DNA (ssDNA) that might be susceptible to cause DNA damage and GCR. Consistently, RNase H expression, which reduces levels of ssDNA, decreased GCRs in cells expressing high level of Spt2p. Lastly, high transcription in the chromosome V, the location at which GCR is monitored, also enhanced GCR formation. We propose a new pathway for GCR where DNA intermediates formed during transcription can lead to genomic instability.
format	article
author	Nilabja Sikdar Soma Banerjee Han Zhang Stephanie Smith Kyungjae Myung
author_facet	Nilabja Sikdar Soma Banerjee Han Zhang Stephanie Smith Kyungjae Myung
author_sort	Nilabja Sikdar
title	Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.
title_short	Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.
title_full	Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.
title_fullStr	Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.
title_full_unstemmed	Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.
title_sort	spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/42073c20706446bf85e29322de1ba02f
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_version_	1718414394702954496

Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway.

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