The Checkpoint Clamp, Rad9-Rad1-Hus1 Complex, Preferentially Stimulates the Activity of Apurinic/apyrimidinic Endonuclease 1 and DNA Polymerase Beta in Long Patch Base Excision Repair

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2007 Apr 12

PMID 17426133

Citations 43

Authors

Agnieszka Gembka

Magali Toueille

Ekaterina Smirnova

Rainer Poltz

Elena Ferrari

Giuseppe Villani

Ulrich Hubscher

Affiliations

Soon will be listed here.

Abstract

Growing evidence suggests that the Rad9-Rad1-Hus1 complex (the 9-1-1 complex), besides its functions in DNA damage sensing and signaling pathways, plays also a direct role in various DNA repair processes. Recent studies have demonstrated that the 9-1-1 complex physically and functionally interacts with several components of the base excision repair (BER) machinery namely DNA polymerase beta (Pol beta), flap endonuclease 1 (Fen 1), DNA ligase I (Lig I) and the MutY homologue of Schizosaccharomyces pombe. In this work, we found for the first time that the 9-1-1 complex interacts in vitro and in vivo with the apurinic/apyrimidinic endonuclease 1 (APE 1), an early component of BER, and can stimulate its AP-endonuclease activity. Moreover, we show that the 9-1-1 complex possesses a stimulatory effect on long patch base excision repair (LP-BER) reconstituted in vitro. The enhancement of LP-BER activity is due to the specific stimulation of the two early components of the repair machinery, namely APE 1 and Pol beta, suggesting a hierarchy of interactions between the 9-1-1 complex and the BER proteins acting in the repairosome. Overall, our results indicate that the 9-1-1 complex is directly involved in LP-BER, thus providing a possible link between DNA damage checkpoints and BER.

Citing Articles

The Role of Protein Arginine Methyltransferases in DNA Damage Response.

Brobbey C, Liu L, Yin S, Gan W Int J Mol Sci. 2022; 23(17).

PMID: 36077176 PMC: 9456308. DOI: 10.3390/ijms23179780.

DNA binding by the Rad9A subunit of the Rad9-Rad1-Hus1 complex.

Hwang B, Gonzales R, Corzine S, Stenson E, Pidugu L, Lu A PLoS One. 2022; 17(8):e0272645.

PMID: 35939452 PMC: 9359528. DOI: 10.1371/journal.pone.0272645.

Mammalian MutY Homolog (MYH or MUTYH) is Critical for Telomere Integrity under Oxidative Stress.

Gupta A, Hwang B, Benyamien-Roufaeil D, Jain S, Liu S, Gonzales R OBM Geriat. 2022; 6(2).

PMID: 35812693 PMC: 9267527. DOI: 10.21926/obm.geriatr.2202196.

ATR signaling in mammalian meiosis: From upstream scaffolds to downstream signaling.

Pereira C, Smolka M, Weiss R, Brieno-Enriquez M Environ Mol Mutagen. 2020; 61(7):752-766.

PMID: 32725817 PMC: 7747128. DOI: 10.1002/em.22401.

Damage sensor role of UV-DDB during base excision repair.

Jang S, Kumar N, Beckwitt E, Kong M, Fouquerel E, Rapic-Otrin V Nat Struct Mol Biol. 2019; 26(8):695-703.

PMID: 31332353 PMC: 6684372. DOI: 10.1038/s41594-019-0261-7.

References

Venclovas C, Thelen M . Structure-based predictions of Rad1, Rad9, Hus1 and Rad17 participation in sliding clamp and clamp-loading complexes. Nucleic Acids Res. 2000; 28(13):2481-93. PMC: 102700. DOI: 10.1093/nar/28.13.2481. View

Prasad R, Dianov G, Bohr V, Wilson S . FEN1 stimulation of DNA polymerase beta mediates an excision step in mammalian long patch base excision repair. J Biol Chem. 2000; 275(6):4460-6. DOI: 10.1074/jbc.275.6.4460. View

Evans A, Kelley M . Going APE over ref-1. Mutat Res. 2000; 461(2):83-108. DOI: 10.1016/s0921-8777(00)00046-x. View

Zhou B, Elledge S . The DNA damage response: putting checkpoints in perspective. Nature. 2000; 408(6811):433-9. DOI: 10.1038/35044005. View

Zhou J, Ahn J, Wilson S, Prives C . A role for p53 in base excision repair. EMBO J. 2001; 20(4):914-23. PMC: 145418. DOI: 10.1093/emboj/20.4.914. View

Podlutsky A, Dianova I, Podust V, Bohr V, Dianov G . Human DNA polymerase beta initiates DNA synthesis during long-patch repair of reduced AP sites in DNA. EMBO J. 2001; 20(6):1477-82. PMC: 145539. DOI: 10.1093/emboj/20.6.1477. View

Offer H, Milyavsky M, Erez N, Matas D, Zurer I, Harris C . Structural and functional involvement of p53 in BER in vitro and in vivo. Oncogene. 2001; 20(5):581-9. DOI: 10.1038/sj.onc.1204120. View

Bermudez V, Lindsey-Boltz L, Cesare A, Maniwa Y, Griffith J, Hurwitz J . Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro. Proc Natl Acad Sci U S A. 2003; 100(4):1633-8. PMC: 149884. DOI: 10.1073/pnas.0437927100. View

Majka J, Burgers P . Yeast Rad17/Mec3/Ddc1: a sliding clamp for the DNA damage checkpoint. Proc Natl Acad Sci U S A. 2003; 100(5):2249-54. PMC: 151326. DOI: 10.1073/pnas.0437148100. View

10.

Meister P, Poidevin M, Francesconi S, Tratner I, Zarzov P, Baldacci G . Nuclear factories for signalling and repairing DNA double strand breaks in living fission yeast. Nucleic Acids Res. 2003; 31(17):5064-73. PMC: 212815. DOI: 10.1093/nar/gkg719. View

11.

Zou L, Liu D, Elledge S . Replication protein A-mediated recruitment and activation of Rad17 complexes. Proc Natl Acad Sci U S A. 2003; 100(24):13827-32. PMC: 283506. DOI: 10.1073/pnas.2336100100. View

12.

Giannattasio M, Lazzaro F, Longhese M, Plevani P, Muzi-Falconi M . Physical and functional interactions between nucleotide excision repair and DNA damage checkpoint. EMBO J. 2004; 23(2):429-38. PMC: 1271758. DOI: 10.1038/sj.emboj.7600051. View

13.

Ellison V, Stillman B . Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA. PLoS Biol. 2003; 1(2):E33. PMC: 261875. DOI: 10.1371/journal.pbio.0000033. View

14.

Friedberg E, McDaniel L, Schultz R . The role of endogenous and exogenous DNA damage and mutagenesis. Curr Opin Genet Dev. 2004; 14(1):5-10. DOI: 10.1016/j.gde.2003.11.001. View

15.

Sancar A, Lindsey-Boltz L, Unsal-Kacmaz K, Linn S . Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004; 73:39-85. DOI: 10.1146/annurev.biochem.73.011303.073723. View

16.

Toueille M, El-Andaloussi N, Frouin I, Freire R, Funk D, Shevelev I . The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilisation efficiency: implications for DNA repair. Nucleic Acids Res. 2004; 32(11):3316-24. PMC: 443528. DOI: 10.1093/nar/gkh652. View

17.

Toueille M, Hubscher U . Regulation of the DNA replication fork: a way to fight genomic instability. Chromosoma. 2004; 113(3):113-25. DOI: 10.1007/s00412-004-0303-7. View

18.

Bartek J, Lukas C, Lukas J . Checking on DNA damage in S phase. Nat Rev Mol Cell Biol. 2004; 5(10):792-804. DOI: 10.1038/nrm1493. View

19.

Sleeth K, Robson R, Dianov G . Exchangeability of mammalian DNA ligases between base excision repair pathways. Biochemistry. 2004; 43(40):12924-30. DOI: 10.1021/bi0492612. View

20.

Matsumoto Y, Kim K . Excision of deoxyribose phosphate residues by DNA polymerase beta during DNA repair. Science. 1995; 269(5224):699-702. DOI: 10.1126/science.7624801. View