Abstract：
:An important feature of poly(ADP-ribose) polymerases (PARPs) is their ability to readily undergo automodification upon activation. Although a growing number of substrates were found to be poly(ADP-ribosyl)ated, including histones and several DNA damage response factors, PARPs themselves are still considered as the main acceptors of poly(ADP-ribose). By monitoring spectral counts of specific hydroxamic acid signatures generated after the conversion of the ADP-ribose modification onto peptides by hydroxylamine hydrolysis, we undertook a thorough mass spectrometry mapping of the glutamate and aspartate ADP-ribosylation sites onto automodified PARP-1, PARP-2 and PARP-3. Thousands of hydroxamic acid-conjugated peptides were identified with high confidence and ranked based on their spectral count. This semi-quantitative approach allowed us to locate the preferentially targeted residues in DNA-dependent PARPs. In contrast to what has been reported in the literature, automodification of PARP-1 is not predominantly targeted towards its BRCT domain. Our results show that interdomain linker regions that connect the BRCT to the WGR module and the WGR to the PRD domain undergo prominent ADP-ribosylation during PARP-1 automodification. We also found that PARP-1 efficiently automodifies the D-loop structure within its own catalytic fold. Interestingly, additional major ADP-ribosylation sites were identified in functional domains of PARP-1, including all three zinc fingers. Similar to PARP-1, specific residues located within the catalytic sites of PARP-2 and PARP-3 are major targets of automodification following their DNA-dependent activation. Together our results suggest that poly(ADP-ribosyl)ation hot spots make a dominant contribution to the overall automodification process.
journal_name
DNA Repair (Amst)journal_title
DNA repairauthors
Gagné JP,Ethier C,Defoy D,Bourassa S,Langelier MF,Riccio AA,Pascal JM,Moon KM,Foster LJ,Ning Z,Figeys D,Droit A,Poirier GGdoi
10.1016/j.dnarep.2015.02.004subject
Has Abstractpub_date
2015-06-01 00:00:00pages
68-79eissn
1568-7864issn
1568-7856pii
S1568-7864(15)00040-3journal_volume
30pub_type
杂志文章相关文献
DNA REPAIR文献大全abstract：:The DNA damage response is a key factor in the maintenance of genome stability. As such, it is a central axis in sustaining cellular homeostasis in a variety of contexts: development, growth, differentiation, and maintenance of the normal life cycle of the cell. It is now clear that diverse mechanisms encompassing cel...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2008.03.005
更新日期：2008-07-01 00:00:00
abstract：:Nijmegen breakage syndrome is a recessive genetic disorder, characterized by elevated sensitivity to ionizing radiation, chromosome instability and high frequency of malignancies. Since cellular features partly overlap with those of ataxia-telangiectasia (A-T), NBS was long considered an A-T clinical variant. NBS1, th...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2004.03.023
更新日期：2004-08-01 00:00:00
abstract：:DNA fiber fluorography is widely employed to study the kinetics of DNA replication, but the usefulness of this approach has been limited by the lack of freely-available automated analysis tools. Quantification of DNA fibers usually relies on manual examination of immunofluorescence microscopy images, which is laboriou...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2019.01.003
更新日期：2019-02-01 00:00:00
abstract：:Methylation of the O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter is associated with G:C to A:T transitions in the p53 gene in various human cancers, including lung cancer. In tumors with p53 mutation, MGMT promoter methylation is more common in advanced tumors than in early tumors. However, in tumors with w...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2008.04.016
更新日期：2008-08-02 00:00:00
abstract：:DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, which if unrepaired or repaired incorrectly can cause cell death or genome instability that may lead to cancer. To counteract these adverse consequences, eukaryotes have evolved a highly orchestrated mechanism to repair DSBs, namely DNA-damage...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2015.04.017
更新日期：2015-08-01 00:00:00
abstract：:Among different DNA repair processes that cells use to face with DNA damage, nucleotide excision repair (NER) is particularly important for the removal of a high variety of lesions, including those generated by some antitumor drugs. A number of factors participating in NER, such as the TFIIH complex and the endonuclea...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2017.01.005
更新日期：2017-03-01 00:00:00
abstract：:DNA-PKcs deficiency has been studied in numerous animal models and cell culture systems. In previous studies of kinase inactivating mutations in cell culture systems, ablation of DNA-PK's catalytic activity results in a cell phenotype that is virtually indistinguishable from that ascribed to complete loss of the enzym...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2018.10.004
更新日期：2019-01-01 00:00:00
abstract：:DNA mismatch repair (MMR) is an evolutionally conserved genome maintenance pathway and is well known for its role in maintaining replication fidelity by correcting biosynthetic errors generated during DNA replication. However, recent studies have shown that MMR preferentially protects actively transcribed genes from m...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2018.08.010
更新日期：2018-11-01 00:00:00
abstract：:Human APOBEC3G (A3G) and activation-induced deaminase (AID) belong to a family of DNA-cytosine deaminases. While A3G targets the last C in a run of C's, AID targets C in the consensus sequence WRC (W is A or T and R is a purine). Guided by the structures of the A3G carboxyl-terminal catalytic domain (A3G-CTD), we iden...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2010.02.010
更新日期：2010-05-04 00:00:00
abstract：:A recently discovered group of novel polymerases are characterized by significantly reduced fidelity of DNA synthesis in vitro. This feature is consistent with the relaxed fidelity required for the replicative bypass of various types of base damage that frequently block high fidelity replicative polymerases. The prese...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/s1568-7864(02)00189-1
更新日期：2003-01-02 00:00:00
abstract：:Deinococcus radiodurans survives extremely high doses of ionizing and ultraviolet radiation and treatment with various DNA-damaging chemicals. As an effort to identify and characterize proteins that function in DNA repair in this organism, we have studied the protein encoded by locus DR1572. This gene is predicted to ...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2008.12.011
更新日期：2009-05-01 00:00:00
abstract：:Mononucleotide microsatellites are tandem repeats of a single base pair, abundant within coding exons and frequent sites of mutation in the human genome. Because the repeated unit is one base pair, multiple mechanisms of insertion/deletion (indel) mutagenesis are possible, including strand-slippage, dNTP-stabilized, a...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2015.02.016
更新日期：2015-05-01 00:00:00
abstract：:Eukaryotic genomes are especially vulnerable to DNA damage during the S phase of the cell cycle, when chromosomes must be duplicated. The stability of DNA replication forks is critical to achieve faithful chromosome replication and is severely compromised when forks encounter DNA lesions. To maintain genome integrity,...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2008.06.014
更新日期：2008-10-01 00:00:00
abstract：:From bacteria to humans, ancient stress responses enable organisms to contend with damage to both the genome and the proteome. These pathways have long been viewed as fundamentally separate responses. Yet recent discoveries from multiple fields have revealed surprising links between the two. Many DNA-damaging agents a...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2018.08.004
更新日期：2018-11-01 00:00:00
abstract：:Like many other cellular processes, regulation of the DNA damage response (DDR) is regulated at different levels, ranging from transcriptional control to an array of distinct post-translational modifications. Involvement of ubiquitylation and the ubiquitin proteasome system in adjusting DDR are such protein modificati...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2007.01.012
更新日期：2007-09-01 00:00:00
abstract：:Neuronal protection induced by ischemic preconditioning has an important role in the reduction of stroke volume and attenuation of neuronal cell death. Ischemic injury is associated with increased oxidative DNA damage, and failure to efficiently repair these oxidatively damaged lesions results in the accumulation of m...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2007.02.027
更新日期：2007-09-01 00:00:00
abstract：:Xeroderma pigmentosum (XP) is a genetic disorder associated with defects in nucleotide excision repair, a pathway that eliminates a wide variety of helix-distorting DNA lesions, including ultraviolet-induced pyrimidine dimers. In addition to skin diseases in sun-exposed areas, approximately 25% of XP patients develop ...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2019.04.004
更新日期：2019-08-01 00:00:00
abstract：:Reactive oxygen species (ROS) are formed as natural byproducts during aerobic metabolism and readily induce premutagenic base lesions in the DNA. The 8-oxoguanine DNA glycosylase (OGG1) and MutY homolog 1 (MYH) synergistically prevent mutagenesis and cancer formation in mice. Their localization in the mitochondria as ...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2011.12.001
更新日期：2012-03-01 00:00:00
abstract：:MutT enzymes prevent DNA damage by hydrolysis of 8-oxodGTP, an oxidized substrate for DNA synthesis and antimutagenic, anticarcinogenic, and antineurodegenerative functions of MutT enzymes are well established. MutT has been found in almost all kingdoms of life, including many bacterial species, yeasts, plants and mam...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2010.10.009
更新日期：2011-02-07 00:00:00
abstract：:Short-wave ultra-violet light promotes the formation of DNA dimers between adjacent thymine bases, and if unrepaired these dimers may induce skin cancer. Living cells have a very robust repair system capable of repairing hundreds of lesions every day. Although many of the details of the dimer repair mechanism are know...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2006.04.007
更新日期：2006-07-13 00:00:00
abstract：:Eukaryotic cells repair ultraviolet light (UV)- and chemical carcinogen-induced DNA strand-distorting damage through the nucleotide excision repair (NER) pathway. Concurrent activation of the DNA damage checkpoints is also required to arrest the cell cycle and allow time for NER action. Recent studies uncovered critic...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2009.01.011
更新日期：2009-04-05 00:00:00
abstract：:In eukaryotic cells, DNA associates with histones and exists in the form of a chromatin hierarchy. Thus, it is generally believed that many eukaryotic cellular DNA processing events such as replication, transcription, recombination and DNA repair are influenced by the packaging of DNA into chromatin. This mini-review ...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2015.09.026
更新日期：2015-12-01 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 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：:Analysis of the spectrum of UV-induced mutations generated in synchronized wild-type S-phase cells reveals that only approximately 25% of mutations occur at thymine (T), whilst 75% are targeted to cytosine (C). The mutational spectra changes dramatically in XP-V cells, devoid of poleta, where approximately 45% of muta...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2005.09.011
更新日期：2006-02-03 00:00:00
abstract：:Eukaryotic genomes are duplicated by a complex machinery, utilizing high fidelity replicative B-family DNA polymerases (pols) α, δ and ε. Specialized error-prone pol ζ, the fourth B-family member, is recruited when DNA synthesis by the accurate trio is impeded by replication stress or DNA damage. The damage tolerance ...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2016.11.004
更新日期：2017-01-01 00:00:00
abstract：:Maintenance of the mitochondrial genome (mtDNA) is essential for proper cellular function. The accumulation of damage and mutations in the mtDNA leads to diseases, cancer, and aging. Mammalian mitochondria have proficient base excision repair, but the existence of other DNA repair pathways is still unclear. Deficienci...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2009.01.021
更新日期：2009-06-04 00:00:00
abstract：:Brh2, the BRCA2 ortholog in the fungus Ustilago maydis, harbors two different DNA-binding domains, one located in the N-terminal region and the other located in the C-terminal region. Here we were interested in comparing the biochemical properties of Brh2 fragments, Brh2(NT) and Brh2(CT), respectively, harboring the t...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2014.07.013
更新日期：2014-10-01 00:00:00
abstract：:Nucleotide excision repair and reversal of pyrimidine dimers by photolyase (photoreactivation) are two major pathways to remove UV-lesions from DNA. Here, it is discussed how lesions are recognized and removed when the DNA is condensed into nucleosomes. During the recent years it was shown that nucleosomes inhibit pho...
journal_title：DNA repair
pub_type： 杂志文章,评审
doi：10.1016/j.dnarep.2005.04.005
更新日期：2005-07-28 00:00:00
abstract：:Ataxia Telangiectasia (A-T) is a progressive childhood disorder characterized most notably by cerebellar degeneration and predisposition to cancer. A-T is caused by mutations in the kinase ATM, a master regulator of the DNA double-strand break response. In addition to DNA-damage signaling defects, A-T cells display mi...
journal_title：DNA repair
pub_type： 杂志文章
doi：10.1016/j.dnarep.2013.11.002
更新日期：2014-01-01 00:00:00
