168
views
0
recommends
+1 Recommend
0 collections
    8
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Human single-stranded DNA binding proteins are essential for maintaining genomic stability

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The double-stranded conformation of cellular DNA is a central aspect of DNA stabilisation and protection. The helix preserves the genetic code against chemical and enzymatic degradation, metabolic activation, and formation of secondary structures. However, there are various instances where single-stranded DNA is exposed, such as during replication or transcription, in the synthesis of chromosome ends, and following DNA damage. In these instances, single-stranded DNA binding proteins are essential for the sequestration and processing of single-stranded DNA. In order to bind single-stranded DNA, these proteins utilise a characteristic and evolutionary conserved single-stranded DNA-binding domain, the oligonucleotide/oligosaccharide-binding (OB)-fold. In the current review we discuss a subset of these proteins involved in the direct maintenance of genomic stability, an important cellular process in the conservation of cellular viability and prevention of malignant transformation. We discuss the central roles of single-stranded DNA binding proteins from the OB-fold domain family in DNA replication, the restart of stalled replication forks, DNA damage repair, cell cycle-checkpoint activation, and telomere maintenance.

          Related collections

          Most cited references248

          • Record: found
          • Abstract: found
          • Article: not found

          Requirement for p53 and p21 to sustain G2 arrest after DNA damage.

          After DNA damage, many cells appear to enter a sustained arrest in the G2 phase of the cell cycle. It is shown here that this arrest could be sustained only when p53 was present in the cell and capable of transcriptionally activating the cyclin-dependent kinase inhibitor p21. After disruption of either the p53 or the p21 gene, gamma radiated cells progressed into mitosis and exhibited a G2 DNA content only because of a failure of cytokinesis. Thus, p53 and p21 appear to be essential for maintaining the G2 checkpoint in human cells.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            DNA double-strand breaks: signaling, repair and the cancer connection.

            To ensure the high-fidelity transmission of genetic information, cells have evolved mechanisms to monitor genome integrity. Cells respond to DNA damage by activating a complex DNA-damage-response pathway that includes cell-cycle arrest, the transcriptional and post-transcriptional activation of a subset of genes including those associated with DNA repair, and, under some circumstances, the triggering of programmed cell death. An inability to respond properly to, or to repair, DNA damage leads to genetic instability, which in turn may enhance the rate of cancer development. Indeed, it is becoming increasingly clear that deficiencies in DNA-damage signaling and repair pathways are fundamental to the etiology of most, if not all, human cancers. Here we describe recent progress in our understanding of how cells detect and signal the presence and repair of one particularly important form of DNA damage induced by ionizing radiation-the DNA double-strand break (DSB). Moreover, we discuss how tumor suppressor proteins such as p53, ATM, Brca1 and Brca2 have been linked to such pathways, and how accumulating evidence is connecting deficiencies in cellular responses to DNA DSBs with tumorigenesis.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Human CtIP promotes DNA end resection.

              In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB resection, and thereby for recruitment of replication protein A (RPA) and the protein kinase ATR to DSBs, and for the ensuing ATR activation. Furthermore, we establish that CtIP physically and functionally interacts with the MRE11 complex, and that both CtIP and MRE11 are required for efficient homologous recombination. Finally, we reveal that CtIP has sequence homology with Sae2, which is involved in MRE11-dependent DSB processing in yeast. These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.
                Bookmark

                Author and article information

                Journal
                BMC Mol Biol
                BMC Mol. Biol
                BMC Molecular Biology
                BioMed Central
                1471-2199
                2013
                1 April 2013
                : 14
                : 9
                Affiliations
                [1 ]Genome Stability Laboratory, Cancer and Ageing Research Program, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Woolloongabba, Queensland, 4102, Australia
                [2 ]School of Science and Health, University of Western Sydney, Sydney, Locked Bag 1797, Penrith, NSW, 2751, Australia
                Article
                1471-2199-14-9
                10.1186/1471-2199-14-9
                3626794
                23548139
                2d242952-b3a7-4cd2-9eb2-2dc3f3c76f2f
                Copyright ©2013 Ashton et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 January 2013
                : 20 March 2013
                Categories
                Review

                Molecular biology
                single-stranded dna binding proteins (ssbs),oligonucleotide/oligosaccharide binding (ob)-fold,double-strand dna break (dsb) repair,homology-directed repair (hdr),translesion synthesis,nucleotide excision repair (ner),replication fork restart,cell cycle checkpoint activation,telomere maintenance

                Comments

                Comment on this article