Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines

Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines

Poly(ADP-ribose) polymerases (PARPs) catalyze poly(ADP-ribose) addition onto proteins, an important posttranslational modification involved in transcription, DNA damage repair, and stem cell identity. Previous studies established the activation of PARP1 in response to DNA damage, but little is known...

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Main Authors: Kristin A. Krukenberg, Ruomu Jiang, Judith A. Steen, Timothy J. Mitchison
Format: Article
Language:English
Published: Elsevier 2014-09-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S221112471400672X
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spelling doaj-9a74eeeafbc34a3989a4ce63c759f0332020-11-24T21:46:48ZengElsevierCell Reports2211-12472014-09-01861808181810.1016/j.celrep.2014.08.009Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell LinesKristin A. Krukenberg0Ruomu Jiang1Judith A. Steen2Timothy J. Mitchison3Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USADepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USAF.M. Kirby Neurobiology Center, Boston Children’s Hospital and Department of Neurology, Harvard Medical School, Boston, MA 02115, USADepartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USAPoly(ADP-ribose) polymerases (PARPs) catalyze poly(ADP-ribose) addition onto proteins, an important posttranslational modification involved in transcription, DNA damage repair, and stem cell identity. Previous studies established the activation of PARP1 in response to DNA damage, but little is known about PARP1 regulation outside of DNA repair. We developed an assay for measuring PARP activity in cell lysates and found that the basal activity of PARP1 was highly variable across breast cancer cell lines, independent of DNA damage. Sucrose gradient fractionation demonstrated that PARP1 existed in at least three biochemically distinct states in both high- and low-activity lines. A discovered complex containing the NuA4 chromatin-remodeling complex and PARP1 was responsible for high basal PARP1 activity, and NuA4 subunits were required for this activity. These findings present a pathway for PARP1 activation and a direct link between PARP1 and chromatin remodeling outside of the DNA damage response.http://www.sciencedirect.com/science/article/pii/S221112471400672X
collection DOAJ
language English
format Article
sources DOAJ
author Kristin A. Krukenberg
Ruomu Jiang
Judith A. Steen
Timothy J. Mitchison
spellingShingle Kristin A. Krukenberg
Ruomu Jiang
Judith A. Steen
Timothy J. Mitchison
Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines
Cell Reports
author_facet Kristin A. Krukenberg
Ruomu Jiang
Judith A. Steen
Timothy J. Mitchison
author_sort Kristin A. Krukenberg
title Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines
title_short Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines
title_full Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines
title_fullStr Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines
title_full_unstemmed Basal Activity of a PARP1-NuA4 Complex Varies Dramatically across Cancer Cell Lines
title_sort basal activity of a parp1-nua4 complex varies dramatically across cancer cell lines
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2014-09-01
description Poly(ADP-ribose) polymerases (PARPs) catalyze poly(ADP-ribose) addition onto proteins, an important posttranslational modification involved in transcription, DNA damage repair, and stem cell identity. Previous studies established the activation of PARP1 in response to DNA damage, but little is known about PARP1 regulation outside of DNA repair. We developed an assay for measuring PARP activity in cell lysates and found that the basal activity of PARP1 was highly variable across breast cancer cell lines, independent of DNA damage. Sucrose gradient fractionation demonstrated that PARP1 existed in at least three biochemically distinct states in both high- and low-activity lines. A discovered complex containing the NuA4 chromatin-remodeling complex and PARP1 was responsible for high basal PARP1 activity, and NuA4 subunits were required for this activity. These findings present a pathway for PARP1 activation and a direct link between PARP1 and chromatin remodeling outside of the DNA damage response.
url http://www.sciencedirect.com/science/article/pii/S221112471400672X
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AT ruomujiang basalactivityofaparp1nua4complexvariesdramaticallyacrosscancercelllines
AT judithasteen basalactivityofaparp1nua4complexvariesdramaticallyacrosscancercelllines
AT timothyjmitchison basalactivityofaparp1nua4complexvariesdramaticallyacrosscancercelllines
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