Abstract:
:In addition to joining broken DNA strands, several non-homologous end-joining (NHEJ) proteins have a second seemingly antithetical role in constructing functional telomeres, the nucleoprotein structures at the termini of linear eukaryotic chromosomes that prevent joining between natural chromosome ends. Although NHEJ deficiency impairs double-strand break (DSB) repair, it also promotes inappropriate chromosomal end fusions that are observed microscopically as dicentric chromosomes with telomeric DNA sequence at points of joining. Here, we test the proposition that unprotected telomeres can fuse not only to other dysfunctional telomeres, but also to ends created by DSBs. Severe combined immunodeficiency (scid) is caused by a mutation in the catalytic subunit of DNA-dependent protein kinase (DNA-PK), an enzyme required for both efficient DSB repair and telomeric end-capping. Cells derived from wild-type, Trp53-/-, scid, and Trp53-/-/scid mice were exposed to gamma radiation to induce DSBs, and chromosomal aberrations were analyzed using a novel cytogenetic technique that can detect joining of a telomere to a DSB end. Telomere-DSB fusions were observed in both cell lines having the scid mutation, but not in wild-type nor Trp53-/- cells. Over a range of 25-340 cGy, half of the visible exchange-type chromosomal aberrations in Trp53-/-/scid cells involved telomere-DSB fusions. Our results demonstrate that unprotected telomeres are not only sensed as, but also acted upon, by the DNA repair machinery as if they were DSB ends. By opening a new pathway for misrepair, telomere-DSB fusion decreases the overall fidelity of DSB repair. The high frequency of these events in scid cells indicates telomere dysfunction makes a strong, and previously unsuspected, contribution to the characteristic radiation sensitivity associated with DNA-PK deficiency.
journal_name
DNA Repair (Amst)journal_title
DNA repairauthors
Bailey SM,Cornforth MN,Ullrich RL,Goodwin EHdoi
10.1016/j.dnarep.2003.11.007keywords:
subject
Has Abstractpub_date
2004-04-01 00:00:00pages
349-57issue
4eissn
1568-7864issn
1568-7856pii
S1568786403002556journal_volume
3pub_type
杂志文章相关文献
DNA REPAIR文献大全abstract::Detection of γ-H2AX foci as a measure of DNA double strand break induction and repair provides the basis of a rapid approach to establish individual radiosensitivity. However, the assignment of criteria to define increased radiosensitivity is not straightforward. Experimental end points, analytical methods and prolife...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2013.07.002
更新日期:2013-10-01 00:00:00
abstract::Me-lex is a sequence-specific alkylating agent synthesized to preferentially (>90%) generate N3-methyladenine (3-mA) in the minor groove of double-strand DNA, in A-T rich regions. In this paper we investigated the effect of XRCC1 deficiency in the processing of 3-mA adducts generated by Me-lex, through the molecular a...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2010.03.016
更新日期:2010-07-01 00:00:00
abstract::In both replicating and non-replicating cells, the maintenance of genomic stability is of utmost importance. Dividing cells can repair DNA damage during cell division, tolerate the damage by employing potentially mutagenic DNA polymerases or die via apoptosis. However, the options for accurate DNA repair are more limi...
journal_title:DNA repair
pub_type: 杂志文章,评审
doi:10.1016/j.dnarep.2019.102669
更新日期:2019-09-01 00:00:00
abstract::In both Schizosaccharomyces pombe and Saccharomyces cerevisiae, Mms22 and Mms1 form a complex with important functions in the response to DNA damage, loss of which leads to perturbations during replication. Furthermore, in S. cerevisiae, Mms1 has been suggested to function in concert with a Cullin-like protein, Rtt101...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2010.11.013
更新日期:2011-03-07 00:00:00
abstract::OGG1 (8-oxoguanine-DNA glycosylase) is the major DNA repair glycosylase removing the premutagenic DNA base modification 8-oxo-7,8-dihydroguanine (8-oxoG) from the genome of mammalian cells. In addition, there is accumulating evidence that OGG1 and its substrate 8-oxoG might function in the regulation of certain genes,...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2017.08.005
更新日期:2017-10-01 00:00:00
abstract::In male germ cells the repair of DNA double strand breaks (DSBs) differs from that described for somatic cell lines. Irradiation induced immunofluorescent foci (IRIF's) signifying a double strand DNA breaks, were followed in spermatogenic cells up to 16 h after the insult. Foci were characterised for Mdc1, 53BP1 and R...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2007.02.011
更新日期:2007-09-01 00:00:00
abstract::The extremely radiation resistant bacterium, Deinococcus radiodurans, contains a spectrum of genes that encode for multiple activities that repair DNA damage. We have cloned and expressed the product of three predicted uracil-DNA glycosylases to determine their biochemical function. DR0689 is a homologue of the Escher...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2003.10.011
更新日期:2004-02-03 00:00:00
abstract::Nucleotide excision repair (NER), cell cycle regulation and apoptosis are major defence mechanisms against the carcinogenic effects of UVB radiation. NER eliminates UVB-induced DNA photolesions via two subpathways: global genome repair (GGR) and transcription-coupled repair (TCR). In a previous study, we found UVB-ind...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2004.08.008
更新日期:2005-01-02 00:00:00
abstract::Proteins that act on DNA, or are in close proximity to it, can become inadvertently crosslinked to DNA and form highly toxic lesions, known as DNA-protein crosslinks (DPCs). DPCs are generated by different chemotherapeutics, environmental or endogenous sources of crosslinking agents, or by lesions on DNA that stall th...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2020.102924
更新日期:2020-10-01 00:00:00
abstract::The human RAD51 recombinase possesses DNA pairing and strand exchange activities that are essential for the error-free, homology-directed repair of DNA double-strand breaks. The recombination activities of RAD51 are activated upon its assembly into presynaptic filaments on single-stranded DNA at resected DSB ends. Def...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2017.10.008
更新日期:2017-12-01 00:00:00
abstract::Early work from about two decades ago implicated DNA double-strand break (DSB) formation and repair in neuronal development. Findings emerging from recent studies of DSBs in proliferating neural progenitors and in mature, non-dividing neurons suggest important roles of DSBs in brain physiology, aging, cancer, psychiat...
journal_title:DNA repair
pub_type: 杂志文章,评审
doi:10.1016/j.dnarep.2018.08.019
更新日期:2018-11-01 00:00:00
abstract::Nucleotide excision repair (NER) is a DNA repair pathway, which eliminates various types of helix-distorting DNA damage including some forms of oxidative damage and UV-induced photoproducts. To understand why patients with NER-defective disorders develop progressive neurological abnormalities, we investigated NER capa...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2006.12.006
更新日期:2007-05-01 00:00:00
abstract::The linear plasmid (pPac1-2) encoded killer toxin (PaT) of the yeast Pichia acaciae arrests sensitive Saccharomyces cerevisiae cells in the S-phase of the cell cycle and induces mutations. Here we provide evidence for opposite effects in PaT resistance of homologous recombination (HR) and non-homologous end joining (N...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2007.07.010
更新日期:2007-12-01 00:00:00
abstract::XPC is one of the key DNA damage recognition proteins in the global genome repair route of the nucleotide excision repair (NER) pathway. Previously, we demonstrated that NER-deficient mouse models Xpa(-/-) and Xpc(-/-) exhibit a divergent spontaneous tumor spectrum and proposed that XPC might be functionally involved ...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2013.08.019
更新日期:2013-12-01 00:00:00
abstract::AHNAK is a high molecular weight protein that is under-expressed in several radiosensitive neuroblastoma cell lines. Using immunoaffinity purification or purified proteins, we show that AHNAK interacts specifically with the DNA ligase IV-XRCC4 complex, a complex that functions in DNA non-homologous end-joining. Furthe...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2003.11.001
更新日期:2004-03-04 00:00:00
abstract::Double-strand breaks (DSBs) are among the most lethal DNA lesions, and a variety of pathways have evolved to manage their repair in a timely fashion. One such pathway is homologous recombination (HR), in which information from an undamaged donor site is used as a template for repair. Although many of the biochemical s...
journal_title:DNA repair
pub_type: 杂志文章,评审
doi:10.1016/j.dnarep.2017.06.012
更新日期:2017-08-01 00:00:00
abstract::The ability of the radiomimetic anti-tumor enediyne C-1027 to induce DNA inter-strand crosslinks (ICLs), in addition to the expected DNA strand breaks, is unique among traditional DNA targeted cancer therapies. Importantly, radiation therapy and most radiomimetic drugs have diminished effect in hypoxic environments du...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2014.06.001
更新日期:2014-09-01 00:00:00
abstract::DNA damage can be considered as a biomarker for toxicity and response to chemotherapy. It is not known whether the chemotherapy-induced genotoxicity is associated with malnutrition. In this pilot study, we assess genotoxicity by means of DNA damage in patients with lymph-node positive colorectal cancer (CRC) and explo...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2018.01.005
更新日期:2018-03-01 00:00:00
abstract::The mechanisms that allow to circumvent replicative stress, and to resume DNA synthesis are poorly understood in Bacillus subtilis. To study the role of the diadenylate cyclase DisA and branch migration translocase (BMT) RadA/Sms in restarting a stalled replication fork, we nicked and broke the circular chromosome of ...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2017.09.006
更新日期:2017-11-01 00:00:00
abstract::Exposure to ionizing radiation results in a variety of genome rearrangements that have been linked to tumor formation. Many of these rearrangements are thought to arise from the repair of double-strand breaks (DSBs) by several mechanisms, including homologous recombination (HR) between repetitive sequences dispersed t...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2008.02.003
更新日期:2008-05-03 00:00:00
abstract::The RecG protein of Escherichia coli is a double-stranded DNA translocase that unwinds a variety of branched DNAs in vitro, including Holliday junctions, replication forks, D-loops and R-loops. Coupled with the reported pleiotropy of recG mutations, this broad range of potential targets has made it hard to pin down wh...
journal_title:DNA repair
pub_type: 杂志文章,评审
doi:10.1016/j.dnarep.2009.12.014
更新日期:2010-03-02 00:00:00
abstract::The bypass of AP sites in yeast requires the Rev1 protein in addition to the Pol ζ translesion synthesis DNA polymerase. Although Rev1 was originally characterized biochemically as a dCMP transferase during AP-site bypass, the relevance of this activity in vivo is unclear. The current study uses highly sensitive frame...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2011.09.017
更新日期:2011-12-10 00:00:00
abstract::A large number of lymphoid malignancies is characterized by specific chromosomal translocations, which are closely linked to the initial steps of pathogenesis. The hallmark of these translocations is the ectopic activation of a silent proto-oncogene through its relocation at the vicinity of an active regulatory elemen...
journal_title:DNA repair
pub_type: 杂志文章,评审
doi:10.1016/j.dnarep.2006.05.015
更新日期:2006-09-08 00:00:00
abstract::Genomic instability has been proposed to play an important role in cancer by accelerating the accumulation of genetic changes responsible for cancer cell evolution. One mechanism for chromosome instability is through the loss of telomeres, which are DNA-protein complexes that protect the ends of chromosomes and preven...
journal_title:DNA repair
pub_type: 杂志文章,评审
doi:10.1016/j.dnarep.2006.05.030
更新日期:2006-09-08 00:00:00
abstract::The continuity of duplex DNA is generally considered a prerequisite for chromosome continuity. However, as previously shown in yeast as well as human cells, the introduction of a double-strand break (DSB) does not generate a chromosome break (CRB) in yeast or human cells. The transition from DSB to CRB was found to be...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2010.10.004
更新日期:2011-01-02 00:00:00
abstract::TFIIH is a multiprotein complex that has a central role in the RNA pol II mediated transcription, in DNA repair and in the control of the cell cycle. Mutations in some components of TFIIH are associated with three hereditary human syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (T...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/s1568-7864(02)00012-5
更新日期:2002-05-30 00:00:00
abstract::In response to the threat of DNA damage, cells exhibit a dramatic and multi-factorial response spanning from transcriptional changes to protein modifications, collectively known as the DNA damage response (DDR). Here, we review the literature surrounding the transcriptional response to DNA damage. We review difference...
journal_title:DNA repair
pub_type: 杂志文章,评审
doi:10.1016/j.dnarep.2019.05.002
更新日期:2019-07-01 00:00:00
abstract::The human gene that encodes XRCC1 was cloned nearly thirty years ago but experimental analysis of this fascinating protein is still unveiling new insights into the DNA damage response. XRCC1 is a molecular scaffold protein that interacts with multiple enzymatic components of DNA single-strand break repair (SSBR) inclu...
journal_title:DNA repair
pub_type: 杂志文章,评审
doi:10.1016/j.dnarep.2019.102664
更新日期:2019-09-01 00:00:00
abstract::Multiple DNA polymerases participate in somatic hypermutation of immunoglobulin (Ig) genes. Mutations at A/T are largely dependent on DNA polymerase eta (POLH) whereas mutations at C/G appear to be generated by several DNA polymerases. We have previously shown that mice expressing a catalytically inactive POLQ (Polq-i...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2006.06.006
更新日期:2006-11-08 00:00:00
abstract::RecQ-like helicases are a highly conserved protein family that functions during DNA repair and, when mutated in humans, is associated with cancer and/or premature aging syndromes. The budding yeast RecQ-like helicase Sgs1 has important functions in double-strand break (DSB) repair of exogenously induced breaks, as wel...
journal_title:DNA repair
pub_type: 杂志文章
doi:10.1016/j.dnarep.2014.12.004
更新日期:2015-02-01 00:00:00