Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break

Polymerase μ (Polμ) participates in the repair of DNA double-strand breaks (DSBs) via the nonhomologous end-joining (NHEJ) pathway. Here, the authors determine the crystal structure of a pre-catalytic ternary complex of human Polμ with a bound DSB substrate and they obtain further mechanistic insigh...

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Main Authors: Andrea M. Kaminski, John M. Pryor, Dale A. Ramsden, Thomas A. Kunkel, Lars C. Pedersen, Katarzyna Bebenek
Format: Article
Language:English
Published: Nature Publishing Group 2020-09-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-020-18506-5
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spelling doaj-08bcf0ae3cab403fbdaf9bdc81fef3242021-09-26T11:46:48ZengNature Publishing GroupNature Communications2041-17232020-09-0111111010.1038/s41467-020-18506-5Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand breakAndrea M. Kaminski0John M. Pryor1Dale A. Ramsden2Thomas A. Kunkel3Lars C. Pedersen4Katarzyna Bebenek5Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, 32-046 Lineberger Comprehensive Cancer CenterCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, 32-046 Lineberger Comprehensive Cancer CenterGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthPolymerase μ (Polμ) participates in the repair of DNA double-strand breaks (DSBs) via the nonhomologous end-joining (NHEJ) pathway. Here, the authors determine the crystal structure of a pre-catalytic ternary complex of human Polμ with a bound DSB substrate and they obtain further mechanistic insights by allowing the insertion reaction to proceed in crystallo, which enabled them to determine a Polμ structure with incomplete incorporation and the structure of the post-catalytic nicked state.https://doi.org/10.1038/s41467-020-18506-5
collection DOAJ
language English
format Article
sources DOAJ
author Andrea M. Kaminski
John M. Pryor
Dale A. Ramsden
Thomas A. Kunkel
Lars C. Pedersen
Katarzyna Bebenek
spellingShingle Andrea M. Kaminski
John M. Pryor
Dale A. Ramsden
Thomas A. Kunkel
Lars C. Pedersen
Katarzyna Bebenek
Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break
Nature Communications
author_facet Andrea M. Kaminski
John M. Pryor
Dale A. Ramsden
Thomas A. Kunkel
Lars C. Pedersen
Katarzyna Bebenek
author_sort Andrea M. Kaminski
title Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break
title_short Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break
title_full Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break
title_fullStr Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break
title_full_unstemmed Structural snapshots of human DNA polymerase μ engaged on a DNA double-strand break
title_sort structural snapshots of human dna polymerase μ engaged on a dna double-strand break
publisher Nature Publishing Group
series Nature Communications
issn 2041-1723
publishDate 2020-09-01
description Polymerase μ (Polμ) participates in the repair of DNA double-strand breaks (DSBs) via the nonhomologous end-joining (NHEJ) pathway. Here, the authors determine the crystal structure of a pre-catalytic ternary complex of human Polμ with a bound DSB substrate and they obtain further mechanistic insights by allowing the insertion reaction to proceed in crystallo, which enabled them to determine a Polμ structure with incomplete incorporation and the structure of the post-catalytic nicked state.
url https://doi.org/10.1038/s41467-020-18506-5
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