Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Ku Autoantigen”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2004

Fluorescence anisotropy studies on the Ku-DNA interaction: anion and cation effects.

DNA non-homologous end joining starts with the binding of Ku heterodimers to double strand breaks. In this work, we characterized the thermodynamics of the Ku-DNA interaction by fluorescence anisotropy of the probe-labeled DNA. We determined that the microscopic dissociation constant (kd) for the binding of Ku to a DNA binding site of the proper length (>20 bp) ranges from 22 to 29 nm at 300 mm NaCl. The binding isotherms for DNA duplexes with two or three heterodimers were analyzed with two independent models considering the presence and absence of overlapping binding sites. This analysis demonstrated that there is no or very weak nearest-neighbor cooperativity among the Ku molecules. These models can most likely be applied to study the interaction of Ku with duplexes of any length. Furthermore, our salt dependence studies indicated that electrostatic interactions play a major role in the binding of Ku to DNA and that the kd decreases approximately 60-fold as the salt concentration is lowered from 300 to 200 mm. The slope (Gammasalt) of the plot of log kd versus log[NaCl] is 12.4 +/- 0.1. This value is among the highest reported in the literature for a protein-DNA interaction and suggests that approximately 12 ions are released upon formation of the Ku-DNA complex. In addition, comparison of the slope values measured upon varying the type of cation and anion indicated that approximately nine cations and three anions are released from DNA and Ku, respectively, when the complex is formed.

Animals↗
PubMed2004

DNA-dependent protein kinase and XRCC4-DNA ligase IV mobilization in the cell in response to DNA double strand breaks.

Repair of DNA double strand breaks (DSBs) by the non-homologous end joining (NHEJ) pathway in mammals requires at least the DNA-dependent protein kinase (DNA-PK) and the DNA ligase IV-XRCC4 protein complexes. DNA-PK comprises the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs. Here we report the first description of the nuclear mobilization of endogenous NHEJ proteins after exposure of human cells to double strand-breaking agents. DSB infliction specifically induced a dose- and time-dependent mobilization of Ku70/80, DNA-PKcs, XRCC4, and DNA ligase IV proteins from a soluble nucleoplasmic compartment to a less extractable nuclear fraction. XRCC4 recruitment was accompanied by its DNA-PK-dependent phosphorylation. The recruited proteins co-immunoprecipitated, indicating that they had assembled into complexes. However, DNA-PK was attached to chromatin, whereas XRCC4-ligase IV resisted solubilization by DNase I. The rates of appearance and dissolution of NHEJ proteins paralleled that of histone variant H2AX phosphorylation and dephosphorylation. We established that under conditions of genomic DSB infliction 1) Ku recruitment was not dependent on the co-recruitment of the other NHEJ proteins, 2) DNA-PKcs was physically required for the mobilization of the XRCC4-ligase IV complex, 3) DNA ligase IV was physically necessary for stable recruitment of XRCC4, and 4) phosphorylation of either H2AX or XRCC4 was unnecessary for DNA-PK or XRCC4-ligase IV recruitment. Altogether these results offer insights into the interplay between key NHEJ proteins during this repair process in the cell.

Antigens, Nuclear↗
PubMed2004

Actinomycin D induces histone gamma-H2AX foci and complex formation of gamma-H2AX with Ku70 and nuclear DNA helicase II.

Formation of gamma-H2AX foci is a P. O.cellular response to genotoxic stress, such as DNA double strand breaks or stalled replication forks. Here we show that gamma-H2AX foci were also formed when cells were incubated with 0.5 microg/ml DNA intercalating agent actinomycin D. In untreated cells, gamma-H2AX co-immunoprecipitated with Ku70, a subunit of DNA-dependent protein kinase, as well as with nuclear DNA helicase II (NDH II), a DEXH family helicase also known as RNA helicase A or DHX9. This association was increased manifold after actinomycin D treatment. DNA degradation diminished the amount of Ku70 associated with gamma-H2AX but not that of NDH II. In vitro binding studies with recombinant NDH II and H2AX phosphorylated by DNA-dependent protein kinase confirmed a direct physical interaction between NDH II and gamma-H2AX. Thereby, the NDH II DEXH domain alone, i.e. its catalytic core, was able to support binding to gamma-H2AX. Congruently, after actinomycin D treatment, NDH II accumulated in RNA-containing nuclear bodies that predominantly co-localized with gamma-H2AX foci. Taken together, these results suggest that histone gamma-H2AX promotes binding of NDH II to transcriptionally stalled sites on chromosomal DNA.

Adenosine Triphosphatases↗
PubMed2005

Regulation of CHK2 by DNA-dependent protein kinase.

Chk2 is a critical mediator of diverse cellular responses to DNA damage. Activation of Chk2 by DNA damage requires phosphorylation at sites including Thr68. In earlier work, we found that an activity present in rabbit reticulocyte lysates phosphorylates and activates Chk2. We now find that hypophosphorylated Chk2 can be phosphorylated at Thr68 by various subcellular fractions of HEK293 cells. This activity is sensitive to the phosphatidylinositol 3'-kinase-like kinase inhibitor wortmannin, but not to caffeine. DNA enhances the Chk2 phosphorylation by cellular fractions in vitro. The wortmannin-sensitive Chk2 kinase activity is present in fractions from ATM-deficient cells. In contrast, Chk2 was not efficiently phosphorylated at Thr68 in vitro by fractions from cells with a defective DNA-dependent protein kinase (DNA-PK) catalytic subunit. Chk2 is phosphorylated by purified DNA-PK in vitro. Endogenous Chk2 coimmunoprecipitates Ku70 and Ku80. In a series of matched cell lines having and lacking functional DNA-PK, Chk2 activation by exposure of cells to ionizing radiation, or to camptothecin was consistently diminished in the absence of DNA-PK. Down-regulation of DNA-PK(cs) by either siRNA or a chemical inhibitor attenuated radiation-induced Chk2 phosphorylation. Ionizing radiation-induced Chk2 phosphorylation was wortmannin-sensitive in ATM-defective cells with depleted ATR. These results suggest that DNA-PK augments ATM and ATR in activation of Chk2 by DNA damage.

Androstadienes↗
PubMed2004

Identification of the polypyrimidine tract binding protein-associated splicing factor.p54(nrb) complex as a candidate DNA double-strand break rejoining factor.

The biological effects of ionizing radiation are attributable, in large part, to induction of DNA double-strand breaks. We report here the identification of a new protein factor that reconstitutes efficient double-strand break rejoining when it is added to a reaction containing the five other polypeptides known to participate in the human nonhomologous end-joining pathway. The factor is a stable heteromeric complex of polypyrimidine tract-binding protein-associated splicing factor (PSF) and a 54-kDa nuclear RNA-binding protein (p54(nrb)). These polypeptides, to which a variety of functions have previously been attributed, share extensive homology, including tandem RNA recognition motif domains. The PSF.p54(nrb) complex cooperates with Ku protein to form a functional preligation complex with substrate DNA. Based on structural comparison with related proteins, we propose a model where the four RNA recognition motif domains in the heteromeric PSF.p54(nrb) complex cooperate to align separate DNA molecules.

Amino Acid Motifs↗
PubMed2005

Ku is a novel transcriptional recycling coactivator of the androgen receptor in prostate cancer cells.

The androgen receptor (AR) dynamically assembles and disassembles multicomponent receptor complexes in order to respond rapidly and reversibly to fluctuations in androgen levels. We are interested in identifying the basal factors that compose the AR aporeceptor and holoreceptor complexes and impact the transcriptional process. Using tandem mass spectroscopy analysis, we identified the trimeric DNA-dependent protein kinase (DNA-PK) complex as the major AR-interacting proteins. AR directly interacts with both Ku70 and Ku80 in vivo and in vitro, as shown by co-immunoprecipitation, glutathione S-transferase pull-down, and Sf9 cell/baculovirus expression. The interaction was localized to the androgen receptor ligand binding domain and is independent of DNA interactions. Ku interacts with AR in the cytoplasm and nucleus regardless of the presence or absence of androgen. Ku acts as a coactivator of AR activity in a luciferase reporter assay employing both Ku-defective cells and Ku small interfering RNA knock-down in a prostate cancer cell line. DNA-PK catalytic subunit (DNA-PKcs) also acts as a coactivator of androgen receptor activity in a luciferase reporter assay employing DNA-PKcs defective cells. AR nuclear translocation is not affected in Ku defective cells, implying Ku functionality may be mainly nuclear. Chromatin immunoprecipitation experiments demonstrated that both Ku70 and Ku80 interact with the prostate-specific antigen promoter in an androgen-dependant manner. Finally, in vitro transcription assays demonstrated Ku involvement in transcriptional recycling with androgen dependent promoters.

Androgens↗
PubMed2005

Modulation of DNA end joining by nuclear proteins.

DNA double strand breaks in mammalian cells are primarily repaired by homologous recombination and non-homologous end joining (NHEJ). NHEJ may either be error-free or mutagenic with deletions or insertions at the joint. Recent studies showed that DNA ends can also be joined via microhomologous sequences flanking the break point especially when proteins responsible for NHEJ, such as Ku, are absent. Microhomology-mediated end joining (MHEJ) is always accompanied by a deletion that spans one of the two homologous sequences and the intervening sequence, if any. In this study we evaluated several factors affecting the relative contribution of MHEJ to DNA end joining using nuclear extracts and DNA substrates containing 10-bp repeats at the ends. We found that the occurrence of MHEJ is determined by the relative abundance of nuclear proteins. At low DNA/protein ratios, an error-free end-joining mechanism predominated over MHEJ. As the DNA/protein ratio increased, MHEJ became predominant. We show that the nuclear proteins that contribute to the inhibition of the error-prone MHEJ include Ku and histone H1. Treatment of extracts with flap endonuclease 1 antiserum significantly reduced MHEJ. Addition of a 17-bp intervening sequence between the microhomologous sequences significantly reduced the efficiency of MHEJ. Thus, this cell-free assay provides a platform for evaluating factors modulating end joining.

Antigens, Nuclear↗
PubMed2005

Regulation of the pancreatic duodenal homeobox-1 protein by DNA-dependent protein kinase.

The transcription factor PDX-1 plays a crucial role during pancreatic development and in the function of insulin-producing beta cells. Disruption of the pdx-1 gene in these cells induces overt diabetes in mice, and this gene is modified in several type 2 diabetic families. It is thus crucial to determine the molecular mechanisms involved in the regulation of PDX-1 expression and/or activation. We identified new proteins associated with PDX-1 by mass spectrometry. These proteins, Ku70 and Ku80, are regulatory subunits of DNA-dependent protein kinase (DNA-PK). We determined that the interaction between PDX-1 and Ku70 or Ku80 is dependent on the homeodomain of PDX-1. Most interestingly, we demonstrated in vitro that the DNA-PK phosphorylates PDX-1 on threonine 11. Although this residue is located in the transactivation domain, this phosphorylation does not seem to be implicated in the transcriptional activation of PDX-1. However, in response to radiation, which activates DNA-PK, a second form of the PDX-1 protein appears rapidly. This form is phosphorylated on threonine and seems to drive PDX-1 degradation by the proteosome. In correlation with this degradation, we observed a subsequent reduction in the activation of the insulin promoter and a decrease in PDX-1-mediated gene expression, i.e. glut2 and glucokinase. Our study demonstrates that radiation, through the activation of DNA-PK, may regulate PDX-1 protein expression.

Amino Acid Sequence↗
PubMed2006

In prostate cancer cells the interaction of C/EBPalpha with Ku70, Ku80, and poly(ADP-ribose) polymerase-1 increases sensitivity to DNA damage.

Prostate cancer cell lines were examined for proteins that partnered with the transcription factor C/EBPalpha by use of a pull-down assay with S-tagged C/EBPalpha combined with matrix-assisted laser desorption ionization time-of-flight mass spectroscopy analysis. Ku70, Ku80, and poly(ADP-ribose) polymerase-1 (PARP-1) were identified as proteins that associated with C/EBPalpha. The physical interaction of C/EBPalpha with these partner proteins was further demonstrated by glutathione S-transferase (GST) pull-downs using purified protein expressed in Escherichia coli. The strongest binding was between C/EBPalpha and PARP-1. Immunoprecipitation of C/EBPalpha expressed in prostate cancer cells co-precipitated Ku70, Ku80, and PARP-1. Deletion analysis of C/EBPalpha indicated that the C terminus of C/EBPalpha was essential for the interaction of C/EBPalpha with Ku70, Ku80, and PARP-1. Functional analysis of the interaction between C/EBPalpha and the Ku proteins as well as PARP-1 showed that cells exhibiting these interactions had increased radiation sensitivity and decreased ability to repair double strand DNA breaks. Deficient DNA repair was dependent on the prostate cancer cell line tested, suggesting a complex process. We conclude that the association of C/EBPalpha with Ku proteins and PARP-1 raises the likelihood that C/EBPalpha-expressing prostate cancer cells may be more sensitive to DNA-damaging agents and may be important in the design of new prostate cancer therapies.

Animals↗
PubMed2006

Kinetic analysis of the Ku-DNA binding activity reveals a redox-dependent alteration in protein structure that stimulates dissociation of the Ku-DNA complex.

Ku is a heterodimeric protein comprising 70- and 80-kDa subunits that participate in the non-homologous end-joining (NHEJ) repair pathway for rejoining DNA double strand breaks. We have analyzed the pre-steady state binding of Ku with various DNA duplex substrates and identified a redox-sensitive Ku-DNA interaction. Pre-steady state analysis of Ku DNA binding was monitored via intrinsic Ku quenching upon binding DNA and revealed that, under fully reduced conditions, binding occurred in a single-step process. Reactions performed under limited reduction revealed a two-step binding process, whereas under fully oxidized conditions, we were unable to detect quenching of Ku fluorescence upon binding DNA. The differential quenching observed under the different redox conditions could not be attributed to two Ku molecules binding to a single substrate or Ku sliding inward on the substrate. Although only modest differences in Ku DNA binding activity were observed in the stoichiometric anisotropy and electrophoretic mobility shift assay studies, as a function of redox conditions, a dramatic difference in the rate of Ku dissociation from DNA was observed. This effect was also induced by diamide treatment of Ku and could be abrogated by dithiothreitol treatment, demonstrating a reversible redox effect on the stability of the Ku-DNA complex. The redox-dependent alteration in Ku-DNA interactions is manifested by a redox-dependent alteration in Ku structure, which was confirmed by limited proteolysis and mass spectrometry analyses. The results support a model for the interaction of Ku with DNA that is regulated by redox status and is achieved by altering the dissociation of the Ku-DNA complex.

DNA↗
PubMed2006

Interplay between Ku, Artemis, and the DNA-dependent protein kinase catalytic subunit at DNA ends.

Repair of DNA double strand breaks (DSB) by the nonhomologous end-joining pathway in mammals requires at least seven proteins involved in a simplified two-step process: (i) recognition and synapsis of the DNA ends dependent on the DNA-dependent protein kinase (DNA-PK) formed by the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs in association with Artemis; (ii) ligation dependent on the DNA ligase IV.XRCC4.Cernunnos-XLF complex. The Artemis protein exhibits exonuclease and endonuclease activities that are believed to be involved in the processing of a subclass of DSB. Here, we have analyzed the interactions of Artemis and nonhomologous end-joining pathway proteins both in a context of human nuclear cell extracts and in cells. DSB-inducing agents specifically elicit the mobilization of Artemis to damaged chromatin together with DNA-PK and XRCC4/ligase IV proteins. DNA-PKcs is necessary for the loading of Artemis on damaged DNA and is the main kinase that phosphorylates Artemis in cells damaged with highly efficient DSB producers. Under kinase-preventive conditions, both in vitro and in cells, Ku-mediated assembly of DNA-PK on DNA ends is responsible for a dissociation of the DNA-PKcs. Artemis complex. Conversely, DNA-PKcs kinase activity prevents Artemis dissociation from the DNA-PK.DNA complex. Altogether, our data allow us to propose a model in which a DNA-PKcs-mediated phosphorylation is necessary both to activate Artemis endonuclease activity and to maintain its association with the DNA end site. This tight functional coupling between the activation of both DNA-PKcs and Artemis may avoid improper processing of DNA.

Amino Acid Sequence↗
PubMed2001

A higher micronucleus yield in B-versus T-cells after low-dose gamma-irradiation is not linked with defective Ku86 protein.

PURPOSE: To elaborate the B-cell micronucleus (MN) response in the low-dose region in detail and to investigate the postulated deficiency in DNA-PK in B-cells. MATERIALS AND METHODS: Lymphocytes of five healthy volunteers were irradiated with low LET gamma-rays and high LET fast neutrons with doses ranging between 0.01 and 2 Gy. After post-irradiation incubation, B- and T-cells were isolated via CD3 and CD19 immunomagnetic microbeads. MN were analysed in both subpopulations. To study the underlying mechanism of chromosomal radiosensitivity, cell extracts prepared from purified B- and T-cells were subjected to SDS-electrophoresis and electroblotting using antibodies directed against the DNA-PK repair enzymes Ku70/86 and DNA-PKcs. Activity measurements were performed using the SignaTECT DNA-dependent protein kinase assay. DNA double-strand break (DSB) induction and rejoining was determined using constant-field gel electrophoresis. RESULTS: For low LET gamma-rays a higher MN yield was observed in B-cells than in T-cells, but only in those samples exposed to doses < 1 Gy. For 1 Gy, the MN yields were comparable and for 2Gy even lower in B-cells compared with T-cells. After high LET neutron irradiation no significant differences in MN yields were observed between both subsets. The results of the DNA-PK experiments demonstrate that there is no difference between T- and B-cells in the basal expression and activity of DNA-PK repair proteins. No differences in DNA DSB induction and rejoining were found between T- and B-cells using constant-field gel electrophoresis. CONCLUSIONS: From the results, it was concluded that the enhanced chromosomal radiosensitivity in B-cells is restricted to low doses (<1 Gy) of low LET radiation and that the chromosomal behaviour of B-cells to low LET radiation cannot be attributed to aberrant forms of the DNA-PK components. A type of chromosomal induced radioresistance (IRR) may be a possible explanation for the observed effect.

Adult↗
PubMed2002

Examining the non-homologous repair process following cisplatin and radiation treatments.

PURPOSE: To investigate the extent of non-homologous end-joining (NHEJ) in the mechanism of cisplatin radiosensitization. MATERIALS AND METHODS: Ku80-deficient cells are deficient in the non-homologous DNA double-strand break repair process, while the wild-type MEF cells maintain full mammalian cell repair capabilities. Both cell lines were exposed to clinically applicable doses of cisplatin (1, 3 and 6 microg x ml(-1)) for 1 h immediately before exposure to 250 kV X-rays. Radiation responses were plotted for each cell line and for all doses of cisplatin to observe relative levels of radiosensitization. Split-dose experiments were also performed on each cell line to measure levels of sublethal damage repair. RESULTS: Radiosensitization was observed in the wild-type cells but not in the Ku80 cells when treated with a combination of 1 microg x ml(-1) cisplatin followed by X-rays, implying that the NHEJ pathway may play a large role in cisplatin radiosensitization. Concurrent administration of this cisplatin dose with radiation produced similar levels of radiosensitization. Conversely, 3 and 6 microg x ml(-1) cisplatin applied immediately before radiation revealed an increasing resistance to radiation in both cell lines--possibly due to resistant subpopulations of cells remaining after subsequent lethal doses of cisplatin. Further experiments revealed that the high concentrations of cisplatin did not alter cell cycle distribution. Finally, split-dose experiments revealed that the NHEJ pathway also plays a significant role in sublethal damage repair. CONCLUSIONS: The study reveals that clinically applicable doses of cisplatin treatment results in the radiosensitization of mammalian cells due to the inhibition of the operation of NHEJ.

Animals↗
PubMed1998

Expression, localization and functional interactions of Ku70 subunit of DNA-PK in peripheral lymphocytes and Nalm-19 cells after irradiation.

PURPOSE: To investigate the changes in expression, localization and functional interaction of Ku70 subunit of DNA-PK after irradiation. MATERIALS AND METHODS: Protein expression by Western blotting, cellular localization by immunofluorescence and functional interactions by immunoprecipitation were investigated after gamma-irradiation in two different cell systems: (1) quiescent human peripheral lymphocytes (0, 2 and 4 Gy) stimulated to proliferate with PHA; and (2) in a proliferating Nalm-19 cell line (0 and 2 Gy). Cell cycle analysis was performed by FACS. Immunofluorescence on extended chromatin fibres was also performed to show close association of Ku70 with the chromatin fibre. RESULTS: Gamma-irradiation induced dose-dependent expression of Ku70 in both cell systems. Confocal microscopy on immunostained cells and cell cycle analysis showed that Ku70 protein translocates to the cytoplasm after the G1 phase. There was a delay in the cytoplasmic shift of Ku70 in the irradiated group, corresponding with the G1 delay. The cytoplasmic localization was supported by ultracentrifugation studies. Immunofluorescence with Ku70 antibody on an extended chromatin fibre showed that Ku70 is closely associated with the chromatin fibre, and irradiation produced many spots of intense fluorescence on it. Ku70 coprecipitated with c-ABL and p21 after irradiation. The c-ABL was coprecipitated throughout the time course of observation, whereas p21 was transiently (0.2 h) associated with Ku70 and only in the lower dose groups. CONCLUSIONS: These studies have demonstrated new biological characteristics of Ku70 in the cellular response to irradiation.

Antigens, Nuclear↗
PubMed1998

Conservation of eukaryotic DNA repair mechanisms.

PURPOSE: To discuss the evolutionary conservation of different DNA repair processes. The proteins that carry out base excision repair show a varying degree of structural conservation, but a high level of functional complementation between species, as might be expected for a sequential pathway. In nucleotide excision repair there is a high degree of structural conservation, but few examples of functional complementation because the process involves multiprotein complexes. Repair by homologous recombination involves proteins that are highly conserved structurally. The process of repair of DNA breaks by non-homologous end-joining is conserved in eukaryotes, but the level of sequence identity of several of the proteins is fairly low and some components involved in man do not appear to have sequence homologues in yeast. CONCLUSIONS: All DNA repair processes are highly conserved. The degree of structural and functional conservation varies between the different processes.

Animals↗
PubMed1998

Reduced joining of DNA double strand breaks with an abnormal mutation spectrum in rodent mutants of DNA-PKcs and Ku80.

PURPOSE: To characterize further the contribution of the DNA-PK-dependent dsb repair pathway in mammalian cells. MATERIALS AND METHODS: The efficiency and fidelity of the joining of linear plasmids by DNA-PKcs-defective mouse cells (SCID) and Ku80-defective Chinese hamster ovary cells (xrs-6) was measured using either linear or circular replicating shuttle vector pZ189. RESULTS: The authors found a 3.9-10.7-fold reduced joining of the DNA ends, as compared with wild-type cells. Mutation analysis of the joining site revealed that the joining process was not hypermutable in the mutated cells. However, the SCID and xrs-6 cells produced a different spectrum of mutations at the joining site with a significantly lower proportion of insertions or more complex mutations. CONCLUSIONS: The remaining joining ability of the mutant cells points to an alternative DNA-PK-independent pathway of dsb repair. Comparison of these data with similar data from yeast suggest that the postulated alternative pathway of dsb repair is at least as efficient and less error-prone in rodent cells.

3T3 Cells↗
PubMed1999

Heat sensitivity of double-stranded DNA-dependent protein kinase (DNA-PK) activity.

PURPOSE: The heat sensitivity of DNA-PK activity in hybrid cells and the possible restoration of this activity with extracts from scid cells (defective in DNA-PKcs), sxi-3 cells (defective in Ku80) and V794 (sxi-3 parental wild-type cells) was analysed. MATERIALS AND METHODS: Heat treatment of cells was performed in a water bath at 44 degrees C. The cell extract from scid cells or sxi-3 cells was added to heat-treated hybrid cell extracts, and the DNA-PK activity was assayed. RESULTS: When hybrid cells were heated at 44 degrees C for 15 min, DNA-PK activity was reduced to undetectable levels. The decreased DNA-PK activity could be restored in a concentration-dependent manner with the addition of scid cell extract. The sxi-3 cell extract could not restore heat-inactivated DNA-PK activity. CONCLUSIONS: DNA-PK was inactivated by heat treatment at 44 degrees C. Ku70/Ku80, but not Ku70 alone, could restore heat-inactivated DNA-PK.

Animals↗
PubMed2006

DNA repair and PARP in aging.

Half a century ago, when the free radical theory of aging was first proposed, the damaging effects of reactive oxygen species (ROS) were in the focus of attention and considered the single most important determinant of aging. Two decades later, however, the disposable soma theory of aging redirected the attention to the potential impact of cellular maintenance and repair pathways that are both genetically and environmentally determined and are counteracting the damaging effects of ROS. In the present paper, recent experimental data linking DNA repair pathways with the aging process are summarised. Special attention is paid to poly(ADP-ribosyl)ation, a DNA-damage driven posttranslational modification of proteins.

Aging↗