CSB interacts with SNM1A and promotes DNA interstrand crosslink processing

Cockayne syndrome (CS) is a premature aging disorder characterized by photosensitivity, impaired development and multisystem progressive degeneration, and consists of two strict complementation groups, A and B. Using a yeast two-hybrid approach, we identified the 5′-3′ exonuclease SNM1A as one of fo...

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Main Authors:	Iyama, Teruaki, Lee, Sook Y., Berquist, Brian R., Gileadi, Opher, Bohr, Vilhelm A., Seidman, Michael M., McHugh, Peter J., Wilson, David M.
Format:	Online
Language:	English
Published:	Oxford University Press 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288174/

id	pubmed-4288174
recordtype	oai_dc
spelling	pubmed-42881742015-02-19 CSB interacts with SNM1A and promotes DNA interstrand crosslink processing Iyama, Teruaki Lee, Sook Y. Berquist, Brian R. Gileadi, Opher Bohr, Vilhelm A. Seidman, Michael M. McHugh, Peter J. Wilson, David M. Genome Integrity, Repair and Replication Cockayne syndrome (CS) is a premature aging disorder characterized by photosensitivity, impaired development and multisystem progressive degeneration, and consists of two strict complementation groups, A and B. Using a yeast two-hybrid approach, we identified the 5′-3′ exonuclease SNM1A as one of four strong interacting partners of CSB. This direct interaction was confirmed using purified recombinant proteins—with CSB able to modulate the exonuclease activity of SNM1A on oligonucleotide substrates in vitro—and the two proteins were shown to exist in a common complex in human cell extracts. CSB and SNM1A were also found, using fluorescently tagged proteins in combination with confocal microscopy and laser microirradiation, to be recruited to localized trioxsalen-induced ICL damage in human cells, with accumulation being suppressed by transcription inhibition. Moreover, SNM1A recruitment was significantly reduced in CSB-deficient cells, suggesting coordination between the two proteins in vivo. CSB-deficient neural cells exhibited increased sensitivity to DNA crosslinking agents, particularly, in a non-cycling, differentiated state, as well as delayed ICL processing as revealed by a modified Comet assay and γ-H2AX foci persistence. The results indicate that CSB coordinates the resolution of ICLs, possibly in a transcription-associated repair mechanism involving SNM1A, and that defects in the process could contribute to the post-mitotic degenerative pathologies associated with CS. Oxford University Press 2015-01-09 2014-12-10 /pmc/articles/PMC4288174/ /pubmed/25505141 http://dx.doi.org/10.1093/nar/gku1279 Text en Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Iyama, Teruaki Lee, Sook Y. Berquist, Brian R. Gileadi, Opher Bohr, Vilhelm A. Seidman, Michael M. McHugh, Peter J. Wilson, David M.
spellingShingle	Iyama, Teruaki Lee, Sook Y. Berquist, Brian R. Gileadi, Opher Bohr, Vilhelm A. Seidman, Michael M. McHugh, Peter J. Wilson, David M. CSB interacts with SNM1A and promotes DNA interstrand crosslink processing
author_facet	Iyama, Teruaki Lee, Sook Y. Berquist, Brian R. Gileadi, Opher Bohr, Vilhelm A. Seidman, Michael M. McHugh, Peter J. Wilson, David M.
author_sort	Iyama, Teruaki
title	CSB interacts with SNM1A and promotes DNA interstrand crosslink processing
title_short	CSB interacts with SNM1A and promotes DNA interstrand crosslink processing
title_full	CSB interacts with SNM1A and promotes DNA interstrand crosslink processing
title_fullStr	CSB interacts with SNM1A and promotes DNA interstrand crosslink processing
title_full_unstemmed	CSB interacts with SNM1A and promotes DNA interstrand crosslink processing
title_sort	csb interacts with snm1a and promotes dna interstrand crosslink processing
description	Cockayne syndrome (CS) is a premature aging disorder characterized by photosensitivity, impaired development and multisystem progressive degeneration, and consists of two strict complementation groups, A and B. Using a yeast two-hybrid approach, we identified the 5′-3′ exonuclease SNM1A as one of four strong interacting partners of CSB. This direct interaction was confirmed using purified recombinant proteins—with CSB able to modulate the exonuclease activity of SNM1A on oligonucleotide substrates in vitro—and the two proteins were shown to exist in a common complex in human cell extracts. CSB and SNM1A were also found, using fluorescently tagged proteins in combination with confocal microscopy and laser microirradiation, to be recruited to localized trioxsalen-induced ICL damage in human cells, with accumulation being suppressed by transcription inhibition. Moreover, SNM1A recruitment was significantly reduced in CSB-deficient cells, suggesting coordination between the two proteins in vivo. CSB-deficient neural cells exhibited increased sensitivity to DNA crosslinking agents, particularly, in a non-cycling, differentiated state, as well as delayed ICL processing as revealed by a modified Comet assay and γ-H2AX foci persistence. The results indicate that CSB coordinates the resolution of ICLs, possibly in a transcription-associated repair mechanism involving SNM1A, and that defects in the process could contribute to the post-mitotic degenerative pathologies associated with CS.
publisher	Oxford University Press
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288174/
_version_	1613174637378666496

CSB interacts with SNM1A and promotes DNA interstrand crosslink processing

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