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The FASEB Journal, Vol 11, 68-76, Copyright © 1997 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins

P Bork, K Hofmann, P Bucher, AF Neuwald, SF Altschul and EV Koonin
European Molecular Biology Laboratory, Heidelberg, Germany.

Computer analysis of a conserved domain, BRCT, first described at the carboxyl terminus of the breast cancer protein BRCA1, a p53 binding protein (53BP1), and the yeast cell cycle checkpoint protein RAD9 revealed a large superfamily of domains that occur predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain consists of approximately 95 amino acid residues and occurs as a tandem repeat at the carboxyl terminus of numerous proteins, but has been observed also as a tandem repeat at the amino terminus or as a single copy. The BRCT superfamily presently includes approximately 40 nonorthologous proteins, namely, BRCA1, 53BP1, and RAD9; a protein family that consists of the fission yeast replication checkpoint protein Rad4, the oncoprotein ECT2, the DNA repair protein XRCC1, and yeast DNA polymerase subunit DPB11; DNA binding enzymes such as terminal deoxynucleotidyltransferases, deoxycytidyl transferase involved in DNA repair, and DNA-ligases III and IV; yeast multifunctional transcription factor RAP1; and several uncharacterized gene products. Another previously described domain that is shared by bacterial NAD-dependent DNA-ligases, the large subunits of eukaryotic replication factor C, and poly(ADP-ribose) polymerases appears to be a distinct version of the BRCT domain. The retinoblastoma protein (a universal tumor suppressor) and related proteins may contain a distant relative of the BRCT domain. Despite the functional diversity of all these proteins, participation in DNA damage-responsive checkpoints appears to be a unifying theme. Thus, the BRCT domain is likely to perform critical, yet uncharacterized, functions in the cell cycle control of organisms from bacteria to humans. The carboxyterminal BRCT domain of BRCA1 corresponds precisely to the recently identified minimal transcription activation domain of this protein, indicating one such function.


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 Mol. Cell. Biol.Home page
K. Liu, F.-T. Lin, J. M. Ruppert, and W.-C. Lin
Regulation of E2F1 by BRCT Domain-Containing Protein TopBP1
Mol. Cell. Biol., May 1, 2003; 23(9): 3287 - 3304.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
Y. Takayama, Y. Kamimura, M. Okawa, S. Muramatsu, A. Sugino, and H. Araki
GINS, a novel multiprotein complex required for chromosomal DNA replication in budding yeast
Genes & Dev., May 1, 2003; 17(9): 1153 - 1165.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y. L. Shang, A. J. Bodero, and P.-L. Chen
NFBD1, a Novel Nuclear Protein with Signature Motifs of FHA and BRCT, and an Internal 41-Amino Acid Repeat Sequence, Is an Early Participant in DNA Damage Response
J. Biol. Chem., February 14, 2003; 278(8): 6323 - 6329.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y. Xia, G. M. Pao, H.-W. Chen, I. M. Verma, and T. Hunter
Enhancement of BRCA1 E3 Ubiquitin Ligase Activity through Direct Interaction with the BARD1 Protein
J. Biol. Chem., February 7, 2003; 278(7): 5255 - 5263.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. S. Williams and J. N. M. Glover
Structural Consequences of a Cancer-causing BRCA1-BRCT Missense Mutation
J. Biol. Chem., January 17, 2003; 278(4): 2630 - 2635.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Lerch-Gaggl, J. Haque, J. Li, G. Ning, P. Traktman, and S. A. Duncan
Pescadillo Is Essential for Nucleolar Assembly, Ribosome Biogenesis, and Mammalian Cell Proliferation
J. Biol. Chem., November 15, 2002; 277(47): 45347 - 45355.
[Abstract] [Full Text] [PDF]

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 ScienceHome page
B. Wang, S. Matsuoka, P. B. Carpenter, and S. J. Elledge
53BP1, a Mediator of the DNA Damage Checkpoint
Science, November 15, 2002; 298(5597): 1435 - 1438.
[Abstract] [Full Text] [PDF]

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 Genome ResHome page
L. Y. Geer, M. Domrachev, D. J. Lipman, and S. H. Bryant
CDART: Protein Homology by Domain Architecture
Genome Res., October 1, 2002; 12(10): 1619 - 1623.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
H. Koiwa, A. W. Barb, L. Xiong, F. Li, M. G. McCully, B.-h. Lee, I. Sokolchik, J. Zhu, Z. Gong, M. Reddy, et al.
C-terminal domain phosphatase-like family members (AtCPLs) differentially regulate Arabidopsis thaliana abiotic stress signaling, growth, and development
PNAS, August 6, 2002; 99(16): 10893 - 10898.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
W. Boner, E. R. Taylor, E. Tsirimonaki, K. Yamane, M. S. Campo, and I. M. Morgan
A Functional Interaction between the Human Papillomavirus 16 Transcription/Replication Factor E2 and the DNA Damage Response Protein TopBP1
J. Biol. Chem., June 14, 2002; 277(25): 22297 - 22303.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
M. A. Marchetti, S. Kumar, E. Hartsuiker, M. Maftahi, A. M. Carr, G. A. Freyer, W. C. Burhans, and J. A. Huberman
A single unbranched S-phase DNA damage and replication fork blockage checkpoint pathway
PNAS, May 28, 2002; 99(11): 7472 - 7477.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. Ramadan, I. V. Shevelev, G. Maga, and U. Hubscher
DNA Polymerase lambda from Calf Thymus Preferentially Replicates Damaged DNA
J. Biol. Chem., May 17, 2002; 277(21): 18454 - 18458.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
H. Yang, B. O. Williams, P. W. Hinds, T. S. Shih, T. Jacks, R. T. Bronson, and D. M. Livingston
Tumor Suppression by a Severely Truncated Species of Retinoblastoma Protein
Mol. Cell. Biol., May 1, 2002; 22(9): 3103 - 3110.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
J.-B. Duvauchelle, L. Blanco, R. P. P. Fuchs, and A. M. Cordonnier
Human DNA polymerase mu (Pol {micro}) exhibits an unusual replication slippage ability at AAF lesion
Nucleic Acids Res., May 1, 2002; 30(9): 2061 - 2067.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. M. Taylor, A. Thistlethwaite, and K. W. Caldecott
Central Role for the XRCC1 BRCT I Domain in Mammalian DNA Single-Strand Break Repair
Mol. Cell. Biol., April 15, 2002; 22(8): 2556 - 2563.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
Y. Kobayashi, M. Watanabe, Y. Okada, H. Sawa, H. Takai, M. Nakanishi, Y. Kawase, H. Suzuki, K. Nagashima, K. Ikeda, et al.
Hydrocephalus, Situs Inversus, Chronic Sinusitis, and Male Infertility in DNA Polymerase {lambda}-Deficient Mice: Possible Implication for the Pathogenesis of Immotile Cilia Syndrome
Mol. Cell. Biol., April 15, 2002; 22(8): 2769 - 2776.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
B. Bertocci, A. De Smet, E. Flatter, A. Dahan, J.-C. Bories, C. Landreau, J.-C. Weill, and C.-A. Reynaud
Cutting Edge: DNA Polymerases {micro} and {lambda} Are Dispensable for Ig Gene Hypermutation
J. Immunol., April 15, 2002; 168(8): 3702 - 3706.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
H. Wang and S. J. Elledge
Genetic and Physical Interactions Between DPB11 and DDC1 in the Yeast DNA Damage Response Pathway
Genetics, April 1, 2002; 160(4): 1295 - 1304.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
W. S. Joo, P. D. Jeffrey, S. B. Cantor, M. S. Finnin, D. M. Livingston, and N. P. Pavletich
Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure
Genes & Dev., March 1, 2002; 16(5): 583 - 593.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. Yamane, X. Wu, and J. Chen
A DNA Damage-Regulated BRCT-Containing Protein, TopBP1, Is Required for Cell Survival
Mol. Cell. Biol., January 15, 2002; 22(2): 555 - 566.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
D. Jullien, P. Vagnarelli, W. C. Earnshaw, and Y. Adachi
Kinetochore localisation of the DNA damage response component 53BP1 during mitosis
J. Cell Sci., January 1, 2002; 115(1): 71 - 79.
[Abstract] [Full Text] [PDF]

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 GeneticsHome page
D. T. Scholes, M. Banerjee, B. Bowen, and M. J. Curcio
Multiple Regulators of Ty1 Transposition in Saccharomyces cerevisiae Have Conserved Roles in Genome Maintenance
Genetics, December 1, 2001; 159(4): 1449 - 1465.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. Taladriz, T. Hanke, M. J. Ramiro, M. Garcia-Diaz, M. Garcia de Lacoba, L. Blanco, and V. Larraga
Nuclear DNA polymerase beta from Leishmania infantum. Cloning, molecular analysis and developmental regulation
Nucleic Acids Res., September 15, 2001; 29(18): 3822 - 3834.
[Abstract] [Full Text] [PDF]


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