Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1

Dragana Ahel; Zuzana Horejsi; Nicola Wiechens; Sophie E. Polo; Elisa Garcia-Wilson; Ivan Ahel; Helen Flynn; Mark Skehel; Stephen C. West; Stephen P. Jackson; Tom Owen-Hughes; Simon J. Boulton

doi:10.1126/science.1177321

Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1

Dragana Ahel, Zuzana Horejsi, Nicola Wiechens, Sophie E. Polo, Elisa Garcia-Wilson, Ivan Ahel, Helen Flynn, Mark Skehel, Stephen C. West, Stephen P. Jackson, Tom Owen-Hughes, Simon J. Boulton

Research output: Contribution to journal › Article › peer-review

487 Citations (Scopus)

Abstract

Posttranslational modifications play key roles in regulating chromatin plasticity. Although various chromatin-remodeling enzymes have been described that respond to specific histone modifications, little is known about the role of poly[adenosine 5'-diphosphate (ADP)-ribose] in chromatin remodeling. Here, we identify a chromatin-remodeling enzyme, ALC1 (Amplified in Liver Cancer 1, also known as CHD1L), that interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding. Our results define ALC1 as a DNA damage-response protein whose role in this process is sustained by its association with known DNA repair factors and its rapid poly(ADP-ribose)-dependent recruitment to DNA damage sites. Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair.

Original language	English
Pages (from-to)	1240-1243
Number of pages	4
Journal	Science
Volume	325
Issue number	5945
DOIs	https://doi.org/10.1126/science.1177321
Publication status	Published - 4 Sept 2009

Keywords

DAMAGE
POLY(ADP-RIBOSYL)ATION
BINDING
POLYNUCLEOSOMES
IDENTIFICATION
RELAXATION
PROTEINS
MOTIFS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/science.1177321

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@article{a4672c6a2f2344fcacdb0bf8102a340d,

title = "Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1",

abstract = "Posttranslational modifications play key roles in regulating chromatin plasticity. Although various chromatin-remodeling enzymes have been described that respond to specific histone modifications, little is known about the role of poly[adenosine 5'-diphosphate (ADP)-ribose] in chromatin remodeling. Here, we identify a chromatin-remodeling enzyme, ALC1 (Amplified in Liver Cancer 1, also known as CHD1L), that interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding. Our results define ALC1 as a DNA damage-response protein whose role in this process is sustained by its association with known DNA repair factors and its rapid poly(ADP-ribose)-dependent recruitment to DNA damage sites. Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair.",

keywords = "DAMAGE, POLY(ADP-RIBOSYL)ATION, BINDING, POLYNUCLEOSOMES, IDENTIFICATION, RELAXATION, PROTEINS, MOTIFS",

author = "Dragana Ahel and Zuzana Horejsi and Nicola Wiechens and Polo, {Sophie E.} and Elisa Garcia-Wilson and Ivan Ahel and Helen Flynn and Mark Skehel and West, {Stephen C.} and Jackson, {Stephen P.} and Tom Owen-Hughes and Boulton, {Simon J.}",

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doi = "10.1126/science.1177321",

language = "English",

volume = "325",

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TY - JOUR

T1 - Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1

AU - Ahel, Dragana

AU - Horejsi, Zuzana

AU - Wiechens, Nicola

AU - Polo, Sophie E.

AU - Garcia-Wilson, Elisa

AU - Ahel, Ivan

AU - Flynn, Helen

AU - Skehel, Mark

AU - West, Stephen C.

AU - Jackson, Stephen P.

AU - Owen-Hughes, Tom

AU - Boulton, Simon J.

PY - 2009/9/4

Y1 - 2009/9/4

N2 - Posttranslational modifications play key roles in regulating chromatin plasticity. Although various chromatin-remodeling enzymes have been described that respond to specific histone modifications, little is known about the role of poly[adenosine 5'-diphosphate (ADP)-ribose] in chromatin remodeling. Here, we identify a chromatin-remodeling enzyme, ALC1 (Amplified in Liver Cancer 1, also known as CHD1L), that interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding. Our results define ALC1 as a DNA damage-response protein whose role in this process is sustained by its association with known DNA repair factors and its rapid poly(ADP-ribose)-dependent recruitment to DNA damage sites. Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair.

AB - Posttranslational modifications play key roles in regulating chromatin plasticity. Although various chromatin-remodeling enzymes have been described that respond to specific histone modifications, little is known about the role of poly[adenosine 5'-diphosphate (ADP)-ribose] in chromatin remodeling. Here, we identify a chromatin-remodeling enzyme, ALC1 (Amplified in Liver Cancer 1, also known as CHD1L), that interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding. Our results define ALC1 as a DNA damage-response protein whose role in this process is sustained by its association with known DNA repair factors and its rapid poly(ADP-ribose)-dependent recruitment to DNA damage sites. Furthermore, we show that depletion or overexpression of ALC1 results in sensitivity to DNA-damaging agents. Collectively, these results provide new insights into the mechanisms by which poly(ADP-ribose) regulates DNA repair.

KW - DAMAGE

KW - POLY(ADP-RIBOSYL)ATION

KW - BINDING

KW - POLYNUCLEOSOMES

KW - IDENTIFICATION

KW - RELAXATION

KW - PROTEINS

KW - MOTIFS

U2 - 10.1126/science.1177321

DO - 10.1126/science.1177321

M3 - Article

C2 - 19661379

SN - 0036-8075

VL - 325

SP - 1240

EP - 1243

JO - Science

JF - Science

IS - 5945

ER -

Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1

Abstract

Keywords

UN SDGs

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