Cooperation of the Cockayne Syndrome Group B Protein and Poly(ADP-ribose) Polymerase 1 in the Response to Oxidative Stress

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2005 Aug 19

PMID 16107709

Citations 66

Authors

Tina Thorslund

Cayetano von Kobbe

Jeanine A Harrigan

Fred E Indig

Mette Christiansen

Tinna Stevnsner

Vilhelm A Bohr

Affiliations

Soon will be listed here.

Abstract

Cockayne syndrome (CS) is a rare genetic disorder characterized as a segmental premature-aging syndrome. The CS group B (CSB) protein has previously been implicated in transcription-coupled repair, transcriptional elongation, and restoration of RNA synthesis after DNA damage. Recently, evidence for a role of CSB in base excision repair of oxidative DNA lesions has accumulated. In our search to understand the molecular function of CSB in this process, we identify a physical and functional interaction between CSB and poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is a nuclear enzyme that protects the integrity of the genome by responding to oxidative DNA damage and facilitating DNA repair. PARP-1 binds to single-strand DNA breaks which activate the catalytic ability of PARP-1 to add polymers of ADP-ribose to various proteins. We find that CSB is present at sites of activated PARP-1 after oxidative stress, identify CSB as a new substrate of PARP-1, and demonstrate that poly(ADP-ribosyl)ation of CSB inhibits its DNA-dependent ATPase activity. Furthermore, we find that CSB-deficient cell lines are hypersensitive to inhibition of PARP. Our results implicate CSB in the PARP-1 poly(ADP-ribosyl)ation response after oxidative stress and thus suggest a novel role of CSB in the cellular response to oxidative damage.

Citing Articles

ATP-Dependent Chromatin Remodeler CSB Couples DNA Repair Pathways to Transcription with Implications for Cockayne Syndrome and Cancer Therapy.

Bilkis R, Lake R, Fan H Cells. 2025; 14(4).

PMID: 39996712 PMC: 11852979. DOI: 10.3390/cells14040239.

Cockayne Syndrome Patient iPSC-Derived Brain Organoids and Neurospheres Show Early Transcriptional Dysregulation of Biological Processes Associated with Brain Development and Metabolism.

Szepanowski L, Wruck W, Kapr J, Rossi A, Fritsche E, Krutmann J Cells. 2024; 13(7.

PMID: 38607030 PMC: 11011893. DOI: 10.3390/cells13070591.

The CSB chromatin remodeler regulates PARP1- and PARP2-mediated single-strand break repair at actively transcribed DNA regions.

Bilkis R, Lake R, Cooper K, Tomkinson A, Fan H Nucleic Acids Res. 2023; 51(14):7342-7356.

PMID: 37326017 PMC: 10415129. DOI: 10.1093/nar/gkad515.

The XPA Protein-Life under Precise Control.

Krasikova Y, Lavrik O, Rechkunova N Cells. 2022; 11(23).

PMID: 36496984 PMC: 9739396. DOI: 10.3390/cells11233723.

Role of Cockayne Syndrome Group B Protein in Replication Stress: Implications for Cancer Therapy.

Walker J, Zhu X Int J Mol Sci. 2022; 23(18).

PMID: 36142121 PMC: 9499456. DOI: 10.3390/ijms231810212.

References

Venema J, Mullenders L, Natarajan A, van Zeeland A, Mayne L . The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA. Proc Natl Acad Sci U S A. 1990; 87(12):4707-11. PMC: 54186. DOI: 10.1073/pnas.87.12.4707. View

Durkacz B, Omidiji O, Gray D, Shall S . (ADP-ribose)n participates in DNA excision repair. Nature. 1980; 283(5747):593-6. DOI: 10.1038/283593a0. View

Giner H, Simonin F, de Murcia G . Overproduction and large-scale purification of the human poly(ADP-ribose) polymerase using a baculovirus expression system. Gene. 1992; 114(2):279-83. DOI: 10.1016/0378-1119(92)90588-g. View

Realini C, Althaus F . Histone shuttling by poly(ADP-ribosylation). J Biol Chem. 1992; 267(26):18858-65. View

Leadon S, Cooper P . Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome. Proc Natl Acad Sci U S A. 1993; 90(22):10499-503. PMC: 47804. DOI: 10.1073/pnas.90.22.10499. View

Caldecott K, Aoufouchi S, Johnson P, Shall S . XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro. Nucleic Acids Res. 1996; 24(22):4387-94. PMC: 146288. DOI: 10.1093/nar/24.22.4387. View

Kubota Y, Nash R, Klungland A, Schar P, Barnes D, Lindahl T . Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. EMBO J. 1996; 15(23):6662-70. PMC: 452490. View

Selby C, Sancar A . Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase but is not a helicase and does not disrupt the ternary transcription complex of stalled RNA polymerase II. J Biol Chem. 1997; 272(3):1885-90. DOI: 10.1074/jbc.272.3.1885. View

Cooper P, Nouspikel T, Clarkson S, Leadon S . Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients from XP group G. Science. 1997; 275(5302):990-3. DOI: 10.1126/science.275.5302.990. View

10.

Masson M, Niedergang C, Schreiber V, Muller S, de Murcia G . XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol Cell Biol. 1998; 18(6):3563-71. PMC: 108937. DOI: 10.1128/MCB.18.6.3563. View

11.

Dianov G, Bischoff C, Sunesen M, Bohr V . Repair of 8-oxoguanine in DNA is deficient in Cockayne syndrome group B cells. Nucleic Acids Res. 1999; 27(5):1365-8. PMC: 148325. DOI: 10.1093/nar/27.5.1365. View

12.

DAmours D, Desnoyers S, DSilva I, Poirier G . Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999; 342 ( Pt 2):249-68. PMC: 1220459. View

13.

Will O, Gocke E, Eckert I, Schulz I, Pflaum M, Mahler H . Oxidative DNA damage and mutations induced by a polar photosensitizer, Ro19-8022. Mutat Res. 1999; 435(1):89-101. DOI: 10.1016/s0921-8777(99)00039-7. View

14.

Kim M, Mauro S, Gevry N, Lis J, Kraus W . NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell. 2004; 119(6):803-14. DOI: 10.1016/j.cell.2004.11.002. View

15.

Meder V, Boeglin M, de Murcia G, Schreiber V . PARP-1 and PARP-2 interact with nucleophosmin/B23 and accumulate in transcriptionally active nucleoli. J Cell Sci. 2004; 118(Pt 1):211-22. DOI: 10.1242/jcs.01606. View

16.

Beerens N, Hoeijmakers J, Kanaar R, Vermeulen W, Wyman C . The CSB protein actively wraps DNA. J Biol Chem. 2004; 280(6):4722-9. DOI: 10.1074/jbc.M409147200. View

17.

Thoma N, Czyzewski B, Alexeev A, Mazin A, Kowalczykowski S, Pavletich N . Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54. Nat Struct Mol Biol. 2005; 12(4):350-6. DOI: 10.1038/nsmb919. View

18.

Farmer H, McCabe N, Lord C, Tutt A, Johnson D, Richardson T . Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434(7035):917-21. DOI: 10.1038/nature03445. View

19.

Durr H, Korner C, Muller M, Hickmann V, Hopfner K . X-ray structures of the Sulfolobus solfataricus SWI2/SNF2 ATPase core and its complex with DNA. Cell. 2005; 121(3):363-73. DOI: 10.1016/j.cell.2005.03.026. View

20.

Le Page F, Kwoh E, Avrutskaya A, Gentil A, Leadon S, Sarasin A . Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome. Cell. 2000; 101(2):159-71. DOI: 10.1016/s0092-8674(00)80827-2. View