11 results match your criteria unhooking review

  • Page 1 of 1

Mechanisms of Vertebrate DNA Interstrand Cross-Link Repair.

Annu Rev Biochem 2021 Jun 21;90:107-135. Epub 2021 Apr 21.

Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA; email:

DNA interstrand cross-links (ICLs) covalently connect the two strands of the double helix and are extremely cytotoxic. Defective ICL repair causes the bone marrow failure and cancer predisposition syndrome, Fanconi anemia, and upregulation of repair causes chemotherapy resistance in cancer. The central event in ICL repair involves resolving the cross-link (unhooking). Read More

View Article and Full-Text PDF

The SNM1A DNA repair nuclease.

DNA Repair (Amst) 2020 11 31;95:102941. Epub 2020 Jul 31.

Department of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS, UK. Electronic address:

Unrepaired, or misrepaired, DNA damage can contribute to the pathogenesis of a number of conditions, or disease states; thus, DNA damage repair pathways, and the proteins within them, are required for the safeguarding of the genome. Human SNM1A is a 5'-to-3' exonuclease that plays a role in multiple DNA damage repair processes. To date, most data suggest a role of SNM1A in primarily ICL repair: SNM1A deficient cells exhibit hypersensitivity to ICL-inducing agents (e. Read More

View Article and Full-Text PDF
November 2020

A role for the base excision repair enzyme NEIL3 in replication-dependent repair of interstrand DNA cross-links derived from psoralen and abasic sites.

DNA Repair (Amst) 2017 04 20;52:1-11. Epub 2017 Feb 20.

University of Missouri Department of Chemistry, 125 Chemistry Building Columbia, MO 65211, United States; University of Missouri Department of Biochemistry, 125 Chemistry Building Columbia, MO 65211, United States. Electronic address:

Interstrand DNA-DNA cross-links are highly toxic lesions that are important in medicinal chemistry, toxicology, and endogenous biology. In current models of replication-dependent repair, stalling of a replication fork activates the Fanconi anemia pathway and cross-links are "unhooked" by the action of structure-specific endonucleases such as XPF-ERCC1 that make incisions flanking the cross-link. This process generates a double-strand break, which must be subsequently repaired by homologous recombination. Read More

View Article and Full-Text PDF

Mechanisms of interstrand DNA crosslink repair and human disorders.

Genes Environ 2016 1;38. Epub 2016 May 1.

Clinical Engineering Research Center, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593 Japan.

Interstrand DNA crosslinks (ICLs) are the link between Watson-Crick strands of DNAs with the covalent bond and prevent separation of DNA strands. Since the ICL lesion affects both strands of the DNA, the ICL repair is not simple. So far, nucleotide excision repair (NER), structure-specific endonucleases, translesion DNA synthesis (TLS), homologous recombination (HR), and factors responsible for Fanconi anemia (FA) are identified to be involved in ICL repair. Read More

View Article and Full-Text PDF

Fanconi anemia: a model disease for studies on human genetics and advanced therapeutics.

Curr Opin Genet Dev 2015 Aug 6;33:32-40. Epub 2015 Aug 6.

Genome Instability and DNA Repair Group, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain. Electronic address:

Fanconi anemia (FA) is characterized by bone marrow failure, malformations, and chromosome fragility. We review the recent discovery of FA genes and efforts to develop genetic therapies for FA in the last five years. Because current data exclude FANCM as an FA gene, 15 genes remain bona fide FA genes and three (FANCO, FANCR and FANCS) cause an FA like syndrome. Read More

View Article and Full-Text PDF

Advances in understanding the complex mechanisms of DNA interstrand cross-link repair.

Cold Spring Harb Perspect Biol 2013 Oct 1;5(10):a012732. Epub 2013 Oct 1.

Department of Microbiology and Molecular Genetics, The University of Pittsburgh, Pittsburgh, Pennsylvania 15219.

DNA interstrand cross-links (ICLs) are lesions caused by a variety of endogenous metabolites, environmental exposures, and cancer chemotherapeutic agents that have two reactive groups. The common feature of these diverse lesions is that two nucleotides on opposite strands are covalently joined. ICLs prevent the separation of two DNA strands and therefore essential cellular processes including DNA replication and transcription. Read More

View Article and Full-Text PDF
October 2013

REV1 and DNA polymerase zeta in DNA interstrand crosslink repair.

Environ Mol Mutagen 2012 Dec 13;53(9):725-40. Epub 2012 Oct 13.

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.

DNA interstrand crosslinks (ICLs) are covalent linkages between two strands of DNA, and their presence interferes with essential metabolic processes such as transcription and replication. These lesions are extremely toxic, and their repair is essential for genome stability and cell survival. In this review, we will discuss how the removal of ICLs requires interplay between multiple genome maintenance pathways and can occur in the absence of replication (replication-independent ICL repair) or during S phase (replication-coupled ICL repair), the latter being the predominant pathway used in mammalian cells. Read More

View Article and Full-Text PDF
December 2012

Multiple roles of ERCC1-XPF in mammalian interstrand crosslink repair.

Environ Mol Mutagen 2010 Jul;51(6):567-81

Department of Carcinogenesis, Science Park-Research Division, University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, USA.

DNA interstrand crosslinks (ICLs) are among the most deleterious cytotoxic lesions encountered by cells, mainly due to the covalent linkage these lesions create between the two strands of DNA which effectively blocks replication and transcription. Although ICL repair in mammalian cells is not fully understood, processing of these lesions is thought to begin by "unhooking" at the site of the damaged base accompanied by the generation of a double strand break and ultimately repair through translesion synthesis and homologous recombination. A key player in this repair process is the heterodimeric protein complex ERCC1-XPF. Read More

View Article and Full-Text PDF

DNA interstrand crosslink repair in mammalian cells: step by step.

Crit Rev Biochem Mol Biol 2010 Feb;45(1):23-49

Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

Interstrand DNA crosslinks (ICLs) are formed by natural products of metabolism and by chemotherapeutic reagents. Work in E. coli identified a two cycle repair scheme involving incisions on one strand on either side of the ICL (unhooking) producing a gapped intermediate with the incised oligonucleotide attached to the intact strand. Read More

View Article and Full-Text PDF
February 2010

Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights.

Mutat Res 2009 Jul 21;668(1-2):54-72. Epub 2009 Feb 21.

Biology and Biotechnology Division, L452, Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551-0808, United States.

The Fanconi anemia (FA) molecular network consists of 15 "FANC" proteins, of which 13 are associated with mutations in patients with this cancer-prone chromosome instability disorder. Whereas historically the common phenotype associated with FA mutations is marked sensitivity to DNA interstrand crosslinking agents, the literature supports a more global role for FANC proteins in coping with diverse stresses encountered by replicative polymerases. We have attempted to reconcile and integrate numerous observations into a model in which FANC proteins coordinate the following physiological events during DNA crosslink repair: (a) activating a FANCM-ATR-dependent S-phase checkpoint, (b) mediating enzymatic replication-fork breakage and crosslink unhooking, (c) filling the resulting gap by translesion synthesis (TLS) by error-prone polymerase(s), and (d) restoring the resulting one-ended double-strand break by homologous recombination repair (HRR). Read More

View Article and Full-Text PDF

Relationship of DNA lesions and their repair to chromosomal aberration production.

M A Bender

Basic Life Sci 1980 ;15:245-65

Though the roles of some specific DNA lesions in the production of chromosomal aberrations is clearly established, those of others remain unclear. While the study of aberration production in human genetic DNA repair deficiency diseases has been extremely rewarding already, eukaryotic repair systems are obviously complex, and one is tempted to feel that such studies may have raised as many questions as they have provided answers. For example, the "standard" sort of xeroderma pigmentosum is chromosomally sensitive to ultraviolet light and to those chemical agents inducing ultraviolet-type DNA repair. Read More

View Article and Full-Text PDF
  • Page 1 of 1