QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cortez, D. Search for Related Content PubMed PubMed Citation Articles by Cortez, D. Related Content DNA Replication, Recombination, and Repair Cell Cycle Social Bookmarking                   What's this?

PERSPECTIVE

Unwind and slow down: checkpoint activation by helicase and polymerase uncoupling

Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, USA

The first 100 words of the full text of this article appear below.

Phosphoinositide 3-kinase related protein kinases (PIKK) including ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK), and ATM and Rad3-related (ATR) coordinate cellular responses to DNA damage. DNA-PK and ATM are primarily activated by double-strand breaks. The ATR kinase, in contrast, responds to numerous forms of genotoxic stress including intrastrand cross-links, oxidative damage, and polymerase toxins. At first glance, the disparate DNA structures that activate ATR impose a difficult biochemical challenge for damage sensing. However, recent data indicate that one DNA structure—single-stranded DNA (ssDNA) coated with a single-stranded DNA-binding protein (RPA)—is a common intermediate to activate ATR signaling in response to all . . . [Full Text of this Article]

	Linking RPA-coated ssDNA to checkpoint kinase activation

 

	How to make RPA–ssDNA

 

	Multiple receptors for the ssDNA–RPA ligand

 

	A second signal for checkpoint activation

 

	Other roles of the MCM complex in checkpoint signaling

 

	Conclusions

 

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X. Zhao, R. J. Madden-Fuentes, B. X. Lou, J. M. Pipas, J. Gerhardt, C. J. Rigell, and E. Fanning Ataxia Telangiectasia-Mutated Damage-Signaling Kinase- and Proteasome-Dependent Destruction of Mre11-Rad50-Nbs1 Subunits in Simian Virus 40-Infected Primate Cells J. Virol., June 1, 2008; 82(11): 5316 - 5328. [Abstract] [Full Text] [PDF]

				K. Sugasawa Xeroderma pigmentosum genes: functions inside and outside DNA repair Carcinogenesis, March 1, 2008; 29(3): 455 - 465. [Abstract] [Full Text] [PDF]

				F. Rodier, J. Campisi, and D. Bhaumik Two faces of p53: aging and tumor suppression Nucleic Acids Res., December 3, 2007; 35(22): 7475 - 7484. [Abstract] [Full Text] [PDF]

				B. E. Weiner, H. Huang, B. M. Dattilo, M. J. Nilges, E. Fanning, and W. J. Chazin An Iron-Sulfur Cluster in the C-terminal Domain of the p58 Subunit of Human DNA Primase J. Biol. Chem., November 16, 2007; 282(46): 33444 - 33451. [Abstract] [Full Text] [PDF]

				J. S. Myers, R. Zhao, X. Xu, A.-J. L. Ham, and D. Cortez Cyclin-Dependent Kinase 2 Dependent Phosphorylation of ATRIP Regulates the G2-M Checkpoint Response to DNA Damage Cancer Res., July 15, 2007; 67(14): 6685 - 6690. [Abstract] [Full Text] [PDF]

				J. R. LaRocque, D. L. Dougherty, S. K. Hussain, and J. Sekelsky Reducing DNA Polymerase {alpha} in the Absence of Drosophila ATR Leads to P53-Dependent Apoptosis and Developmental Defects Genetics, July 1, 2007; 176(3): 1441 - 1451. [Abstract] [Full Text] [PDF]

				H. L. Ball, M. R. Ehrhardt, D. A. Mordes, G. G. Glick, W. J. Chazin, and D. Cortez Function of a Conserved Checkpoint Recruitment Domain in ATRIP Proteins Mol. Cell. Biol., May 1, 2007; 27(9): 3367 - 3377. [Abstract] [Full Text] [PDF]

				C. A. MacDougall, T. S. Byun, C. Van, M.-c. Yee, and K. A. Cimprich The structural determinants of checkpoint activation Genes & Dev., April 15, 2007; 21(8): 898 - 903. [Abstract] [Full Text] [PDF]

				P. S. Levitt, M. Zhu, A. Cassano, S. A. Yazinski, H. Liu, J. Darfler, R. M. Peters, and R. S. Weiss Genome Maintenance Defects in Cultured Cells and Mice following Partial Inactivation of the Essential Cell Cycle Checkpoint Gene Hus1 Mol. Cell. Biol., March 15, 2007; 27(6): 2189 - 2201. [Abstract] [Full Text] [PDF]

				F. Marini, T. Nardo, M. Giannattasio, M. Minuzzo, M. Stefanini, P. Plevani, and M. M. Falconi DNA nucleotide excision repair-dependent signaling to checkpoint activation PNAS, November 14, 2006; 103(46): 17325 - 17330. [Abstract] [Full Text] [PDF]

				E. S. Zimmerman, M. P. Sherman, J. L. Blackett, J. A. Neidleman, C. Kreis, P. Mundt, S. A. Williams, M. Warmerdam, J. Kahn, F. M. Hecht, et al. Human Immunodeficiency Virus Type 1 Vpr Induces DNA Replication Stress In Vitro and In Vivo J. Virol., November 1, 2006; 80(21): 10407 - 10418. [Abstract] [Full Text] [PDF]

				D. J. Chang, P. J. Lupardus, and K. A. Cimprich Monoubiquitination of Proliferating Cell Nuclear Antigen Induced by Stalled Replication Requires Uncoupling of DNA Polymerase and Mini-chromosome Maintenance Helicase Activities J. Biol. Chem., October 27, 2006; 281(43): 32081 - 32088. [Abstract] [Full Text] [PDF]

				D. E. Wilkinson and S. K. Weller Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection J. Cell Sci., July 1, 2006; 119(13): 2695 - 2703. [Abstract] [Full Text] [PDF]

				T. Silva, R. H. Bradley, Y. Gao, and M. Coue Xenopus CDC7/DRF1 Complex Is Required for the Initiation of DNA Replication J. Biol. Chem., April 28, 2006; 281(17): 11569 - 11576. [Abstract] [Full Text] [PDF]

				J. S. Myers and D. Cortez Rapid Activation of ATR by Ionizing Radiation Requires ATM and Mre11 J. Biol. Chem., April 7, 2006; 281(14): 9346 - 9350. [Abstract] [Full Text] [PDF]

				P. J. Lupardus and K. A. Cimprich Phosphorylation of Xenopus Rad1 and Hus1 Defines a Readout for ATR Activation That Is Independent of Claspin and the Rad9 Carboxy Terminus Mol. Biol. Cell, April 1, 2006; 17(4): 1559 - 1569. [Abstract] [Full Text] [PDF]

				G. Jiang and A. Sancar Recruitment of DNA Damage Checkpoint Proteins to Damage in Transcribed and Nontranscribed Sequences Mol. Cell. Biol., January 1, 2006; 26(1): 39 - 49. [Abstract] [Full Text] [PDF]

				H. L. Ball and D. Cortez ATRIP Oligomerization Is Required for ATR-dependent Checkpoint Signaling J. Biol. Chem., September 9, 2005; 280(36): 31390 - 31396. [Abstract] [Full Text] [PDF]