For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
39
views
61
references
 Top references
cited by
24
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      335
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Structure-dependent bypass of DNA interstrand crosslinks by translesion synthesis polymerases

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      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

          DNA interstrand crosslinks (ICLs), inhibit DNA metabolism by covalently linking two strands of DNA and are formed by antitumor agents such as cisplatin and nitrogen mustards. Multiple complex repair pathways of ICLs exist in humans that share translesion synthesis (TLS) past a partially processed ICL as a common step. We have generated site-specific major groove ICLs and studied the ability of Y-family polymerases and Pol ζ to bypass ICLs that induce different degrees of distortion in DNA. Two main factors influenced the efficiency of ICL bypass: the length of the dsDNA flanking the ICL and the length of the crosslink bridging two bases. Our study shows that ICLs can readily be bypassed by TLS polymerases if they are appropriately processed and that the structure of the ICL influences which polymerases are able to read through it.

          Related collections

          Most cited references61

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

          Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function.

          Satya Prakash, Robert Johnson, Louise Prakash (2005)
          This review focuses on eukaryotic translesion synthesis (TLS) DNA polymerases, and the emphasis is on Saccharomyces cerevisiae and human Y-family polymerases (Pols) eta, iota, kappa, and Rev1, as well as on Polzeta, which is a member of the B-family polymerases. The fidelity, mismatch extension ability, and lesion bypass efficiencies of these different polymerases are examined and evaluated in the context of their structures. One major conclusion is that, despite the overall similarity of basic structural features among the Y-family polymerases, there is a high degree of specificity in their lesion bypass properties. Some are able to bypass a particular DNA lesion, whereas others are efficient at only the insertion step or the extension step of lesion bypass. This functional divergence is related to the differences in their structures. Polzeta is a highly specialized polymerase specifically adapted for extending primer termini opposite from a diverse array of DNA lesions, and depending upon the DNA lesion, it contributes to lesion bypass in a mutagenic or in an error-free manner. Proliferating cell nuclear antigen (PCNA) provides the central scaffold to which TLS polymerases bind for access to the replication ensemble stalled at a lesion site, and Rad6-Rad18-dependent protein ubiquitination is important for polymerase exchange.
          Article 0 comments Cited 249 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.

            Puck Knipscheer, Markus Räschle, Agata Smogorzewska … (2009)
            Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.
            Article 0 comments Cited 178 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              How the fanconi anemia pathway guards the genome.

              George-Lucian Moldovan, Alan D'Andrea (2009)
              Fanconi Anemia (FA) is an inherited genomic instability disorder, caused by mutations in genes regulating replication-dependent removal of interstrand DNA crosslinks. The Fanconi Anemia pathway is thought to coordinate a complex mechanism that enlists elements of three classic DNA repair pathways, namely homologous recombination, nucleotide excision repair, and mutagenic translesion synthesis, in response to genotoxic insults. To this end, the Fanconi Anemia pathway employs a unique nuclear protein complex that ubiquitinates FANCD2 and FANCI, leading to formation of DNA repair structures. Lack of obvious enzymatic activities among most FA members has made it challenging to unravel its precise modus operandi. Here we review the current understanding of how the Fanconi Anemia pathway components participate in DNA repair and discuss the mechanisms that regulate this pathway to ensure timely, efficient, and correct restoration of chromosomal integrity.
              Article 0 comments Cited 168 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Nucleic Acids Res
                Journal ID (publisher-id): nar
                Journal ID (hwp): nar
                Title: Nucleic Acids Research
                Publisher: Oxford University Press
                ISSN (Print): 0305-1048
                ISSN (Electronic): 1362-4962
                Publication date Collection: September 2011
                Publication date (Print): September 2011
                Publication date (Electronic): 11 June 2011
                Publication date PMC-release: 11 June 2011
                Volume: 39
                Issue: 17
                Pages: 7455-7464
                Affiliations
                1Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794-3400, USA, 2Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland and 3Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA
                Author notes
                *To whom correspondence should be addressed. Tel: +1 631 632 7545; Fax: +1 631 632 7546; Email: orlando@ 123456pharm.stonybrook.edu
                Article
                Publisher ID: gkr448
                DOI: 10.1093/nar/gkr448
                PMC ID: 3177197
                PubMed ID: 21666254
                SO-VID: 76a0a7ca-cc13-42d1-bcc1-3bfe70181f39
                Copyright © © The Author(s) 2011. Published by Oxford University Press.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 4 November 2010
                Date revision received : 15 May 2011
                Date accepted : 16 May 2011
                Page count
                Pages: 10
                Categories
                Subject: Genome Integrity, Repair and Replication

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

                Comments

                Comment on this article

                scite_

                Similar content335

                See all similar

                Cited by24

                See all cited by

                Most referenced authors1,431

                See all reference authors