An inactivated nuclease-like domain in RecC with novel function: implications for evolution

Rigden, Daniel John
January 2005
BMC Structural Biology;2005, Vol. 5, p9
Academic Journal
Background: The PD-(D/E)xK superfamily, containing a wide variety of other exo- and endonucleases, is a notable example of general function conservation in the face of extreme sequence and structural variation. Almost all members employ a small number of shared conserved residues to bind catalytically essential metal ions and thereby effect DNA cleavage. The crystal structure of the RecBCD prokaryotic DNA repair machinery shows that RecB contains such a nuclease domain at its C-terminus. The RecC C-terminal region was reported as having a novel fold. Results: The RecC C-terminal region can be divided into an alpha/beta domain and a smaller alphahelical bundle domain. Here we show that the alpha/beta domain is homologous to the RecB nuclease domain but lacks the features necessary for catalysis. Instead, the domain has a novel function within the nuclease superfamily - providing a hoop through which single-stranded DNA passes. Comparison with other structures of nuclease domains bound to DNA reveals strikingly different modes of ligand binding. The alpha-helical bundle domain contributes the pin which splits the DNA duplex. Conclusion: The demonstrated homology of RecB and RecC shows how evolution acted to produce the present RecBCD complex through aggregation of new domains as well as functional divergence and structural redeployment of existing domains. Distantly homologous nuclease(-like) domains bind DNA in highly diverse manners.


Related Articles

  • Interaction of Flap Endonuclease-1 and Replication Protein A with Photoreactive Intermediates of DNA Repair. Nazarkina, J. K.; Petrousseva, I. O.; Safronov, I. V.; Lavrik, O. I.; Khodyreva, S. N. // Biochemistry (00062979);Aug2003, Vol. 68 Issue 8, p934 

    A new method for enzymatic synthesis of radioactive DNA flapped structures containing a photoreactive dCMP moiety at a branch point with 4-(4-azido-2,3,5,6-tetrafluorobenzylidene-hydrazinocarbonyl)butylcarbamoyl group attached at exo-N-position of cytosine was developed. The formation of...

  • Drug-induced cell cycle modulation leading to cell-cycle arrest, nuclear mis-segregation, or endoreplication. Sakaue-Sawano, Asako; Kobayashi, Tamiyo; Ohtawa, Kenji; Miyawaki, Atsushi // BMC Cell Biology;2011, Vol. 12 Issue 1, p2 

    Background: Cancer cell responses to chemotherapeutic agents vary, and this may reflect different defects in DNA repair, cell-cycle checkpoints, and apoptosis control. Cytometry analysis only quantifies dye-incorporation to examine DNA content and does not reflect the biological complexity of...

  • Spatio-temporal analysis of DNA damage repair using the X-ray microbeam. Schettino, G.; Ghita, M.; Prise, K. M. // European Physical Journal D -- Atoms, Molecules, Clusters & Opti;Nov2010, Vol. 60 Issue 1, p157 

    Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organization is still unclear despite its decisive role in determining the fate of the damaged cell. The single-cell approach and the high spatial resolution offered by...

  • A model for dsDNA translocation revealed by a structural motif common to RecG and Mfd proteins. Mahdi, Akeel A.; Briggs, Geoffrey S.; Sharples, Gary J.; Qin Wen; Lloyd, Robert G. // EMBO Journal;2/1/2003, Vol. 22 Issue 3, p724 

    RecG protein differs from other helicases analysed to atomic resolution in that it mediates strand separation via translocation on double-stranded (ds) rather than single-stranded (ss) DNA. We describe a highly conserved helical hairpin motif in RecG and show it to be important for helicase...

  • The RABiT: high-throughput technology for assessing global DSB repair. Turner, Helen; Sharma, P.; Perrier, J.; Bertucci, A.; Smilenov, L.; Johnson, G.; Taveras, M.; Brenner, D.; Garty, G. // Radiation & Environmental Biophysics;May2014, Vol. 53 Issue 2, p265 

    At the Center for High-Throughput Minimally Invasive Radiation Biodosimetry, we have developed a rapid automated biodosimetry tool (RABiT); this is a completely automated, ultra-high-throughput robotically based biodosimetry workstation designed for use following a large-scale radiological...

  • DNA helicases involved in DNA repair and their roles in cancer. Brosh, Robert M. // Nature Reviews Cancer;Aug2013, Vol. 13 Issue 8, p542 

    Helicases have major roles in genome maintenance by unwinding structured nucleic acids. Their prominence is marked by various cancers and genetic disorders that are linked to helicase defects. Although considerable effort has been made to understand the functions of DNA helicases that are...

  • Structure and conformational dynamics of base excision repair DNA glycosylases. Zharkov, D. O. // Molecular Biology;Sep2007, Vol. 41 Issue 5, p702 

    DNA glycosylases play a key role in DNA repair, which maintains the integrity of the cell genome. The structures of many DNA glycosylases have been solved to date. The review considers these structures and the dynamics of DNA glycosylase interactions with DNA. The available data suggest that...

  • A closed conformation for the Pol?catalytic cycle. Garcia-Diaz, Miguel; Bebenek, Katarzyna; Krahn, Joseph M.; Kunkel, Thomas A.; Pedersen, Lars C. // Nature Structural & Molecular Biology;Jan2005, Vol. 12 Issue 1, p97 

    Pol?is a family X member believed to fill short gaps during DNA repair. Here we report crystal structures of Pol?representing three steps in filling a single-nucleotide gap. These structures indicate that, unlike other DNA polymerases, Pol?does not undergo large subdomain movements during...

  • Cell biology: Holding sisters for repair. Hirano, Tatsuya // Nature;2/3/2005, Vol. 433 Issue 7025, p467 

    This article presents information related to DNA replication and DNA repair. Before a cell divides, it must replicate its DNA, producing two identical copies of each chromosome, known as sister chromatids. In this process, information on the undamaged sister is used as a template for repair....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics