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Science 10 July 1998:
Vol. 281. no. 5374, pp. 272 - 274
DOI: 10.1126/science.281.5374.272
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Reports

Rad53 FHA Domain Associated with Phosphorylated Rad9 in the DNA Damage Checkpoint

Zhaoxia Sun, James Hsiao, David S. Fay, * David F. Stern dagger

The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA. The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated Rad9 interacted with the COOH-terminal forkhead homology-associated (FHA) domain of Rad53. Inactivation of this domain abolished DNA damage-dependent Rad53 phosphorylation, G2/M cell cycle phase arrest, and increase of RNR3 transcription but did not affect replication inhibition-dependent Rad53 phosphorylation. Thus, Rad53 integrates DNA damage signals by coupling with phosphorylated Rad9. The hitherto uncharacterized FHA domain appears to be a modular protein-binding domain.

Z. Sun, Department of Biology, Yale University, New Haven, CT 06511, USA, and Department of Pathology, Yale School of Medicine, 310 Cedar Street, Room BML 342, New Haven, CT 06520-8023, USA. J. Hsiao, D. S. Fay, D. F. Stern, Department of Pathology,Yale School of Medicine, 310 Cedar Street, Room BML 342, New Haven, CT 06520-8023, USA.
*   Present address: Room B058, Porter Biosciences, MCD Biology, University of Colorado, Boulder, CO 80309-0347, USA.

dagger    To whom correspondence should be addressed. E-mail: Stern{at}biomed.med.yale.edu

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The FHA Domain, a Phosphoamino Acid Binding Domain Involved in the DNA Damage Response Pathway.
M. HUANG and S.J. ELLEDGE (2000)
Cold Spring Harb Symp Quant Biol 65, 413-422
   Abstract »    PDF »
The FHA Domain in DNA Repair and Checkpoint Signaling.
D. DUROCHER, S.J. SMERDON, M.B. YAFFE, and S.P. JACKSON (2000)
Cold Spring Harb Symp Quant Biol 65, 423-432
   Abstract »    PDF »
Details and Concerns Regarding the G2/M DNA Damage Checkpoint in Budding Yeast.
T. WEINERT, E. LITTLE, L. SHANKS, A. ADMIRE, R. GARDNER, C. PUTNAM, R. MICHELSON, K. NYBERG, and P. SUNDARESHAN (2000)
Cold Spring Harb Symp Quant Biol 65, 433-442
   Abstract »    PDF »
The DNA Damage Checkpoint and Human Cancer.
L.B. SCHULTZ, N.H. CHEHAB, A. MALIKZAY, R.A. DITULLIO, E.S. STAVRIDI, and T.D. HALAZONETIS (2000)
Cold Spring Harb Symp Quant Biol 65, 489-498
   Abstract »    PDF »
Interactions of the Nijmegen Breakage Syndrome Protein with ATM and BRCA1.
X. WU, G. RATHBUN, W.S. LANE, D.T. WEAVER, and D.M. LIVINGSTON (2000)
Cold Spring Harb Symp Quant Biol 65, 535-546
   Abstract »    PDF »
The Function of BRCA1 in DNA Damage Response.
J.-S. LEE, K. COLLINS, A. BROWN, C.-H. LEE, and J.H. CHUNG (2000)
Cold Spring Harb Symp Quant Biol 65, 547-552
   Abstract »    PDF »
Heterozygous Germ Line hCHK2 Mutations in Li-Fraumeni Syndrome.
D. W. Bell, J. M. Varley, T. E. Szydlo, D. H. Kang, D. C. Wahrer, K. E. Shannon, M. Lubratovich, S. J. Verselis, K. J. Isselbacher, J. F. Fraumeni, et al. (1999)
Science 286, 2528-2531
   Abstract »    Full Text »
The protein kinases of Caenorhabditis elegans: A model for signal transduction in multicellular organisms.
G. D. Plowman, S. Sudarsanam, J. Bingham, D. Whyte, and T. Hunter (1999)
PNAS 96, 13603-13610
   Abstract »    Full Text »    PDF »
Control of the DNA Damage Checkpoint by Chk1 and Rad53 Protein Kinases Through Distinct Mechanisms.
Y. Sanchez, J. Bachant, H. Wang, F. Hu, D. Liu, M. Tetzlaff, and S. J. Elledge (1999)
Science 286, 1166-1171
   Abstract »    Full Text »


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