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Structure specific DNA recognition by the SLX1–SLX4 endonuclease complex

The SLX1–SLX4 structure-specific endonuclease complex is involved in processing diverse DNA damage intermediates, including resolution of Holliday junctions, collapse of stalled replication forks and removal of DNA flaps. The nuclease subunit SLX1 is inactive on its own, but become activated upon bi...

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Autores principales: Xu, Xiang, Wang, Mingzhu, Sun, Jixue, Yu, Zhenyu, Li, Guohong, Yang, Na, Xu, Rui-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287910/
https://www.ncbi.nlm.nih.gov/pubmed/34181713
http://dx.doi.org/10.1093/nar/gkab542
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author Xu, Xiang
Wang, Mingzhu
Sun, Jixue
Yu, Zhenyu
Li, Guohong
Yang, Na
Xu, Rui-Ming
author_facet Xu, Xiang
Wang, Mingzhu
Sun, Jixue
Yu, Zhenyu
Li, Guohong
Yang, Na
Xu, Rui-Ming
author_sort Xu, Xiang
collection PubMed
description The SLX1–SLX4 structure-specific endonuclease complex is involved in processing diverse DNA damage intermediates, including resolution of Holliday junctions, collapse of stalled replication forks and removal of DNA flaps. The nuclease subunit SLX1 is inactive on its own, but become activated upon binding to SLX4 via its conserved C-terminal domain (CCD). Yet, how the SLX1–SLX4 complex recognizes specific DNA structure and chooses cleavage sites remains unknown. Here we show, through a combination of structural, biochemical and computational analyses, that the SAP domain of SLX4 is critical for efficient and accurate processing of 5′-flap DNA. It binds the minor groove of DNA about one turn away from the flap junction, and the 5′-flap is implicated in binding the core domain of SLX1. This binding mode accounts for specific recognition of 5′-flap DNA and specification of cleavage site by the SLX1–SLX4 complex.
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spelling pubmed-82879102021-07-19 Structure specific DNA recognition by the SLX1–SLX4 endonuclease complex Xu, Xiang Wang, Mingzhu Sun, Jixue Yu, Zhenyu Li, Guohong Yang, Na Xu, Rui-Ming Nucleic Acids Res Structural Biology The SLX1–SLX4 structure-specific endonuclease complex is involved in processing diverse DNA damage intermediates, including resolution of Holliday junctions, collapse of stalled replication forks and removal of DNA flaps. The nuclease subunit SLX1 is inactive on its own, but become activated upon binding to SLX4 via its conserved C-terminal domain (CCD). Yet, how the SLX1–SLX4 complex recognizes specific DNA structure and chooses cleavage sites remains unknown. Here we show, through a combination of structural, biochemical and computational analyses, that the SAP domain of SLX4 is critical for efficient and accurate processing of 5′-flap DNA. It binds the minor groove of DNA about one turn away from the flap junction, and the 5′-flap is implicated in binding the core domain of SLX1. This binding mode accounts for specific recognition of 5′-flap DNA and specification of cleavage site by the SLX1–SLX4 complex. Oxford University Press 2021-06-28 /pmc/articles/PMC8287910/ /pubmed/34181713 http://dx.doi.org/10.1093/nar/gkab542 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Xu, Xiang
Wang, Mingzhu
Sun, Jixue
Yu, Zhenyu
Li, Guohong
Yang, Na
Xu, Rui-Ming
Structure specific DNA recognition by the SLX1–SLX4 endonuclease complex
title Structure specific DNA recognition by the SLX1–SLX4 endonuclease complex
title_full Structure specific DNA recognition by the SLX1–SLX4 endonuclease complex
title_fullStr Structure specific DNA recognition by the SLX1–SLX4 endonuclease complex
title_full_unstemmed Structure specific DNA recognition by the SLX1–SLX4 endonuclease complex
title_short Structure specific DNA recognition by the SLX1–SLX4 endonuclease complex
title_sort structure specific dna recognition by the slx1–slx4 endonuclease complex
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287910/
https://www.ncbi.nlm.nih.gov/pubmed/34181713
http://dx.doi.org/10.1093/nar/gkab542
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