Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

J. Biol. Chem. 278 (52): 52914-52918

© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphopeptide Binding Specificities of BRCA1 COOH-terminal (BRCT) Domains*

Maria Rodriguez{ddagger}§, Xiaochun Yu¶§, Junjie Chen¶, , and Zhou Songyang{ddagger}||

{ddagger}Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 and the Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905

Abstract: Protein phosphorylation by protein kinases may generate docking sites for other proteins. It thus allows the assembly of signaling complexes in response to kinase activation. Several protein domains that bind phosphoserine or phosphothreonine residues have been identified, including the 14-3-3, PIN1, FHA, KIX, WD-40 domain, and polo box (Yaffe, M. B., and Elia, A. E. (2001) Curr. Opin. Cell Biol. 13, 131-138; Elia, A. E., Cantley, L. C., and Yaffe, M. B. (2003) Science 299, 1228-1231). The BRCA1 COOH-terminal (BRCT) domains are protein modules found in many proteins that regulate DNA damage responses (Koonin, E. V., Altschul, S. F., and Bork, P. (1996) Nat. Genet. 13, 266-268). Whether BRCT domains can mediate phosphorylation-dependent interactions has not been systematically investigated. We report here that the BRCT domains also recognize phosphopeptides. Oriented peptide library analysis indicated that the BRCT domains from BRCA1, MDC1, BARD1, and DNA Ligase IV preferred distinct phosphoserine-containing peptides. In addition, the interaction between BRCA1 and the BRCT binding motif of BACH1 was required for BACH1 checkpoint activity. Furthermore, BRCT domains of the yeast DNA repair protein Rad9 could bind phosphopeptides, suggesting that the BRCT domains represent a class of ancient phosphopeptide-binding modules. Potential targets of BRCT domains were identified through data base search. Structural analysis of BRCA1 BRCT repeats also predicted conserved residues that may form the phosphopeptide-binding pocket. Thus, the BRCT repeats are a new family of phosphopeptide-binding domains in DNA damage responses.

Received for publication September 9, 2003. Revision received October 16, 2003.

* This work was supported by Department of Defense Breast Cancer Idea Award DAMD 17-01-1-0145 (to Z. S.), by the Robert Welch Foundation (to Z. S.), and by Initiative for Minority Student Development Grant GM569209 (to M. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ These authors contributed equally.

|| To whom correspondence should be addressed: Verna and Marrs McLean Dept. of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail: songyang{at}bcm.tmc.edu.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Dual Interaction between the DNA Damage Response Protein MDC1 and the RAG1 Subunit of the V(D)J Recombinase.
G. Coster, A. Gold, D. Chen, D. G. Schatz, and M. Goldberg (2012)
J. Biol. Chem. 287, 36488-36498
   Abstract »    Full Text »    PDF »
Charting the Landscape of Tandem BRCT Domain-Mediated Protein Interactions.
N. T. Woods, R. D. Mesquita, M. Sweet, M. A. Carvalho, X. Li, Y. Liu, H. Nguyen, C. E. Thomas, E. S. Iversen Jr., S. Marsillac, et al. (2012)
Science Signaling 5, rs6
   Abstract »    Full Text »    PDF »
Molecular Basis for the Association of Microcephalin (MCPH1) Protein with the Cell Division Cycle Protein 27 (Cdc27) Subunit of the Anaphase-promoting Complex.
N. Singh, T. D. Wiltshire, J. R. Thompson, G. Mer, and F. J. Couch (2012)
J. Biol. Chem. 287, 2854-2862
   Abstract »    Full Text »    PDF »
Yeast two-hybrid junk sequences contain selected linear motifs.
Y. Liu, N. T. Woods, D. Kim, M. Sweet, A. N. A. Monteiro, and R. Karchin (2011)
Nucleic Acids Res. 39, e128
   Abstract »    Full Text »    PDF »
Molecular Basis of BACH1/FANCJ Recognition by TopBP1 in DNA Replication Checkpoint Control.
C. C. Y. Leung, Z. Gong, J. Chen, and J. N. M. Glover (2011)
J. Biol. Chem. 286, 4292-4301
   Abstract »    Full Text »    PDF »
Tandem BRCT Domains: DNA's Praetorian Guard.
R. D. Mesquita, N. T. Woods, E. S. Seabra-Junior, and A. N. A. Monteiro (2010)
Genes & Cancer 1, 1140-1146
   Abstract »    Full Text »    PDF »
Toward Classification of BRCA1 Missense Variants Using a Biophysical Approach.
P. J. E. Rowling, R. Cook, and L. S. Itzhaki (2010)
J. Biol. Chem. 285, 20080-20087
   Abstract »    Full Text »    PDF »
Comprehensive Analysis of Missense Variations in the BRCT Domain of BRCA1 by Structural and Functional Assays.
M. S. Lee, R. Green, S. M. Marsillac, N. Coquelle, R. S. Williams, T. Yeung, D. Foo, D. D. Hau, B. Hui, A. N. A. Monteiro, et al. (2010)
Cancer Res. 70, 4880-4890
   Abstract »    Full Text »    PDF »
Structural and Functional Interaction between the Human DNA Repair Proteins DNA Ligase IV and XRCC4.
P.-Y. Wu, P. Frit, S. Meesala, S. Dauvillier, M. Modesti, S. N. Andres, Y. Huang, J. Sekiguchi, P. Calsou, B. Salles, et al. (2009)
Mol. Cell. Biol. 29, 3163-3172
   Abstract »    Full Text »    PDF »
Somatic hypermutation of immunoglobulin genes: lessons from proliferating cell nuclear antigenK164R mutant mice.
P. Langerak, P. H.L Krijger, M. R Heideman, P. C.M van den Berk, and H. Jacobs (2009)
Phil Trans R Soc B 364, 621-629
   Abstract »    Full Text »    PDF »
Histone Ubiquitination Associates with BRCA1-Dependent DNA Damage Response.
J. Wu, M. S. Y. Huen, L.-Y. Lu, L. Ye, Y. Dou, M. Ljungman, J. Chen, and X. Yu (2009)
Mol. Cell. Biol. 29, 849-860
   Abstract »    Full Text »    PDF »
The Direct Interaction between 53BP1 and MDC1 Is Required for the Recruitment of 53BP1 to Sites of Damage.
Y. Eliezer, L. Argaman, A. Rhie, A. J. Doherty, and M. Goldberg (2009)
J. Biol. Chem. 284, 426-435
   Abstract »    Full Text »    PDF »
{gamma}-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin.
A. Kinner, W. Wu, C. Staudt, and G. Iliakis (2008)
Nucleic Acids Res. 36, 5678-5694
   Abstract »    Full Text »    PDF »
Evidence for a Structural Relationship between BRCT Domains and the Helicase Domains of the Replication Initiators Encoded by the Polyomaviridae and Papillomaviridae Families of DNA Tumor Viruses.
A. Kumar, W. S. Joo, G. Meinke, S. Moine, E. N. Naumova, and P. A. Bullock (2008)
J. Virol. 82, 8849-8862
   Abstract »    Full Text »    PDF »
Early events in the mammalian response to DNA double-strand breaks.
L. C. Riches, A. M. Lynch, and N. J. Gooderham (2008)
Mutagenesis 23, 331-339
   Abstract »    Full Text »    PDF »
RAP80 Responds to DNA Damage Induced by Both Ionizing Radiation and UV Irradiation and Is Phosphorylated at Ser205.
J. Yan, X.-P. Yang, Y.-S. Kim, and A. M. Jetten (2008)
Cancer Res. 68, 4269-4276
   Abstract »    Full Text »    PDF »
A common SNP of MCPH1 is associated with cranial volume variation in Chinese population.
J.-k. Wang, Y. Li, and B. Su (2008)
Hum. Mol. Genet. 17, 1329-1335
   Abstract »    Full Text »    PDF »
Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.
B. Wang and S. J. Elledge (2007)
PNAS 104, 20759-20763
   Abstract »    Full Text »    PDF »
Structural Requirements for the BARD1 Tumor Suppressor in Chromosomal Stability and Homology-directed DNA Repair.
M. Laufer, S. V. Nandula, A. P. Modi, S. Wang, M. Jasin, V. V. V. S. Murty, T. Ludwig, and R. Baer (2007)
J. Biol. Chem. 282, 34325-34333
   Abstract »    Full Text »    PDF »
The DNA Damage Response Mediator MDC1 Directly Interacts with the Anaphase-promoting Complex/Cyclosome.
G. Coster, Z. Hayouka, L. Argaman, C. Strauss, A. Friedler, M. Brandeis, and M. Goldberg (2007)
J. Biol. Chem. 282, 32053-32064
   Abstract »    Full Text »    PDF »
The ePHD protein SPBP interacts with TopBP1 and together they co-operate to stimulate Ets1-mediated transcription.
E. Sjottem, C. Rekdal, G. Svineng, S. S. Johnsen, H. Klenow, R. D. Uglehus, and T. Johansen (2007)
Nucleic Acids Res. 35, 6648-6662
   Abstract »    Full Text »    PDF »
Activation of BRCA1/BRCA2-Associated Helicase BACH1 Is Required for Timely Progression through S Phase.
E. Kumaraswamy and R. Shiekhattar (2007)
Mol. Cell. Biol. 27, 6733-6741
   Abstract »    Full Text »    PDF »
NFBD1/MDC1 Associates with p53 and Regulates Its Function at the Crossroad between Cell Survival and Death in Response to DNA Damage.
M. Nakanishi, T. Ozaki, H. Yamamoto, T. Hanamoto, H. Kikuchi, K. Furuya, M. Asaka, D. Delia, and A. Nakagawara (2007)
J. Biol. Chem. 282, 22993-23004
   Abstract »    Full Text »    PDF »
Abraxas and RAP80 Form a BRCA1 Protein Complex Required for the DNA Damage Response.
B. Wang, S. Matsuoka, B. A. Ballif, D. Zhang, A. Smogorzewska, S. P. Gygi, and S. J. Elledge (2007)
Science 316, 1194-1198
   Abstract »    Full Text »    PDF »
An optimized method for detecting gamma-H2AX in blood cells reveals a significant interindividual variation in the gamma-H2AX response among humans.
I. H. Ismail, T. I. Wadhra, and O. Hammarsten (2007)
Nucleic Acids Res. 35, e36
   Abstract »    Full Text »    PDF »
Determination of Cancer Risk Associated with Germ Line BRCA1 Missense Variants by Functional Analysis.
M. A. Carvalho, S. M. Marsillac, R. Karchin, S. Manoukian, S. Grist, R. F. Swaby, T. P. Urmenyi, E. Rondinelli, R. Silva, L. Gayol, et al. (2007)
Cancer Res. 67, 1494-1501
   Abstract »    Full Text »    PDF »
BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP..
X. Yu, S. Fu, M. Lai, R. Baer, and J. Chen (2006)
Genes & Dev. 20, 1721-1726
   Abstract »    Full Text »    PDF »
BRCA1 Promotes Induction of ssDNA by Ionizing Radiation..
B. P. Schlegel, F. M. Jodelka, and R. Nunez (2006)
Cancer Res. 66, 5181-5189
   Abstract »    Full Text »    PDF »
Identification of Domains of BRCA1 Critical for the Ubiquitin-Dependent Inhibition of Centrosome Function..
S. Sankaran, L. M. Starita, A. M. Simons, and J. D. Parvin (2006)
Cancer Res. 66, 4100-4107
   Abstract »    Full Text »    PDF »
BRCA1 Affects Lipid Synthesis through Its Interaction with Acetyl-CoA Carboxylase.
K. Moreau, E. Dizin, H. Ray, C. Luquain, E. Lefai, F. Foufelle, M. Billaud, G. M. Lenoir, and N. D. Venezia (2006)
J. Biol. Chem. 281, 3172-3181
   Abstract »    Full Text »    PDF »
The Fanconi Anemia/BRCA pathway: new faces in the crowd.
R. D. Kennedy and A. D. D'Andrea (2005)
Genes & Dev. 19, 2925-2940
   Abstract »    Full Text »    PDF »
Structure of the BRCT Repeat Domain of MDC1 and Its Specificity for the Free COOH-terminal End of the {gamma}-H2AX Histone Tail.
M. S. Lee, R. A. Edwards, G. L. Thede, and J. N. M. Glover (2005)
J. Biol. Chem. 280, 32053-32056
   Abstract »    Full Text »    PDF »
53BP1 exchanges slowly at the sites of DNA damage and appears to require RNA for its association with chromatin.
F. Pryde, S. Khalili, K. Robertson, J. Selfridge, A.-M. Ritchie, D. W. Melton, D. Jullien, and Y. Adachi (2005)
J. Cell Sci. 118, 2043-2055
   Abstract »    Full Text »    PDF »
SIRT1 Shows No Substrate Specificity in Vitro.
G. Blander, J. Olejnik, E. Krzymanska-Olejnik, T. McDonagh, M. Haigis, M. B. Yaffe, and L. Guarente (2005)
J. Biol. Chem. 280, 9780-9785
   Abstract »    Full Text »    PDF »
The BRCA1 RING and BRCT Domains Cooperate in Targeting BRCA1 to Ionizing Radiation-induced Nuclear Foci.
W. W. Y. Au and B. R. Henderson (2005)
J. Biol. Chem. 280, 6993-7001
   Abstract »    Full Text »    PDF »
DNA-dependent Protein Kinase and XRCC4-DNA Ligase IV Mobilization in the Cell in Response to DNA Double Strand Breaks.
J. Drouet, C. Delteil, J. Lefrancois, P. Concannon, B. Salles, and P. Calsou (2005)
J. Biol. Chem. 280, 7060-7069
   Abstract »    Full Text »    PDF »
The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis.
J. G. Jansen, A. Tsaalbi-Shtylik, P. Langerak, F. Calléja, C. M. Meijers, H. Jacobs, and N. de Wind (2005)
Nucleic Acids Res. 33, 356-365
   Abstract »    Full Text »    PDF »
Viral Transport of DNA Damage That Mimics a Stalled Replication Fork.
J. Jurvansuu, K. Raj, A. Stasiak, and P. Beard (2005)
J. Virol. 79, 569-580
   Abstract »    Full Text »    PDF »
Exploiting the DNA Repair Defect in BRCA Mutant Cells in the Design of New Therapeutic Strategies for Cancer.
A.N.J. TUTT, C.J. LORD, N. MCCABE, H. FARMER, N. TURNER, N.M. MARTIN, S.P. JACKSON, G.C.M. SMITH, and A. ASHWORTH (2005)
Cold Spring Harb Symp Quant Biol 70, 139-148
   Abstract »    PDF »
DNA Damage-Induced Cell Cycle Checkpoint Control Requires CtIP, a Phosphorylation-Dependent Binding Partner of BRCA1 C-Terminal Domains.
X. Yu and J. Chen (2004)
Mol. Cell. Biol. 24, 9478-9486
   Abstract »    Full Text »    PDF »
Phosphorylation and Regulation of DNA Ligase IV Stability by DNA-dependent Protein Kinase.
Y.-G. Wang, C. Nnakwe, W. S. Lane, M. Modesti, and K. M. Frank (2004)
J. Biol. Chem. 279, 37282-37290
   Abstract »    Full Text »    PDF »
Microcephalin Is a DNA Damage Response Protein Involved in Regulation of CHK1 and BRCA1.
X. Xu, J. Lee, and D. F. Stern (2004)
J. Biol. Chem. 279, 34091-34094
   Abstract »    Full Text »    PDF »
Histone H2A Phosphorylation Controls Crb2 Recruitment at DNA Breaks, Maintains Checkpoint Arrest, and Influences DNA Repair in Fission Yeast.
T. M. Nakamura, L.-L. Du, C. Redon, and P. Russell (2004)
Mol. Cell. Biol. 24, 6215-6230
   Abstract »    Full Text »    PDF »
The Human Rap1 Protein Complex and Modulation of Telomere Length.
M. S. O'Connor, A. Safari, D. Liu, J. Qin, and Z. Songyang (2004)
J. Biol. Chem. 279, 28585-28591
   Abstract »    Full Text »    PDF »
BRCA1 Interacts with and Is Required for Paclitaxel-Induced Activation of Mitogen-Activated Protein Kinase Kinase Kinase 3.
P. M. Gilmore, N. McCabe, J. E. Quinn, R. D. Kennedy, J. J. Gorski, H. N. Andrews, S. McWilliams, M. Carty, P. B. Mullan, W. P. Duprex, et al. (2004)
Cancer Res. 64, 4148-4154
   Abstract »    Full Text »    PDF »
Cellular machineries for chromosomal DNA repair.
C. L. Peterson and J. Cote (2004)
Genes & Dev. 18, 602-616
   Full Text »    PDF »
TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival.
K. Liu, Y. Luo, F.-T. Lin, and W.-C. Lin (2004)
Genes & Dev. 18, 673-686
   Abstract »    Full Text »    PDF »
2003: Signaling Breakthroughs of the Year.
E. M. Adler, N. R. Gough, and L. B. Ray (2004)
Sci. STKE 2004, eg1
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882