scholarly journals Loss of DNA repair capacity during successive subcultures of primary rat fibroblasts.

1977 ◽  
Vol 74 (2) ◽  
pp. 365-370 ◽  
Author(s):  
A C Chan ◽  
I G Walker
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Strand Break ◽  
Single Strand ◽  
Velocity Sedimentation ◽  
Early Passage ◽  
Repair Capacity ◽  
Repair Synthesis ◽  
Single Strand Break ◽  
Passage Cells

Cultures of fibroblasts from newborn rats and successive subcultures of these cells were treated with 4-nitroquinoline-1-oxide to induce DNA repair. DNA from the cultures was examined by velocity sedimentation in alkaline sucrose gradients immediately after drug treatment and after a post-treatment incubation period of 3 h. Early passage cells were able to repair the damage that appeared as single strand breaks, however, by the seventh subculture this activity was not apparent. Measurements of repair synthesis showed a partial loss of this capacity with successive subculture. The results fit a model in which 4NQO causes two kinds of DNA modification, one of which is alkali labile and appears as a single-strand break. Both modifications are subject to excision repair, but each is recognized initially by a specific endonuclease. In the late passage cells, the endonuclease specific for the alkali labile modification is absent.

scholarly journals Distinct spatiotemporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair

2013 ◽  
Vol 41 (5) ◽  
pp. 3115-3129 ◽  
Author(s):  
Anna Campalans ◽  
Thierry Kortulewski ◽  
Rachel Amouroux ◽  
Hervé Menoni ◽  
Wim Vermeulen ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Strand Break ◽  
Single Strand ◽  
Spatiotemporal Patterns ◽  
Single Strand Break ◽  
Base Excision

scholarly journals XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair

2021 ◽  
Author(s):  
Marek Adamowicz ◽  
Richard Hailstone ◽  
Annie A. Demin ◽  
Emilia Komulainen ◽  
Hana Hanzlikova ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Neurological Disease ◽  
Excision Repair ◽  
Strand Break ◽  
Single Strand ◽  
Toxic Activity ◽  
Single Strand Break ◽  
Dna Base Excision Repair ◽  
Dna Base ◽  
Base Excision

AbstractGenetic defects in the repair of DNA single-strand breaks (SSBs) can result in neurological disease triggered by toxic activity of the single-strand-break sensor protein PARP1. However, the mechanism(s) by which this toxic PARP1 activity triggers cellular dysfunction are unclear. Here we show that human cells lacking XRCC1 fail to rapidly recover transcription following DNA base damage, a phenotype also observed in patient-derived fibroblasts with XRCC1 mutations and Xrcc1−/− mouse neurons. This defect is caused by excessive/aberrant PARP1 activity during DNA base excision repair, resulting from the loss of PARP1 regulation by XRCC1. We show that aberrant PARP1 activity suppresses transcriptional recovery during base excision repair by promoting excessive recruitment and activity of the ubiquitin protease USP3, which as a result reduces the level of monoubiquitinated histones important for normal transcriptional regulation. Importantly, inhibition and/or deletion of PARP1 or USP3 restores transcriptional recovery in XRCC1−/− cells, highlighting PARP1 and USP3 as possible therapeutic targets in neurological disease.

scholarly journals Age, sex, and race influence single-strand break repair capacity in a human population

2008 ◽  
Vol 45 (12) ◽  
pp. 1631-1641 ◽  
Author(s):  
Andrzej R. Trzeciak ◽  
Janice Barnes ◽  
Ngozi Ejiogu ◽  
Kamala Foster ◽  
Larry J. Brant ◽  
...  
Keyword(s):  
Human Population ◽  
Strand Break ◽  
Single Strand ◽  
Repair Capacity ◽  
Single Strand Break ◽  
Single Strand Break Repair ◽  
Break Repair

Xeroderma pigmentosum D-HeLa hybrids with low and high ultraviolet sensitivity associated with normal and diminished DNA repair ability, respectively

1985 ◽  
Vol 76 (1) ◽  
pp. 115-133
Author(s):  
R.T. Johnson ◽  
S. Squires ◽  
G.C. Elliott ◽  
G.L. Koch ◽  
A.J. Rainbow
Keyword(s):  
Dna Repair ◽  
Xeroderma Pigmentosum ◽  
Excision Repair ◽  
Complementation Group ◽  
Repair Capacity ◽  
Repair Synthesis ◽  
Repair Ability ◽  
Dna Repair Synthesis ◽  
Host Cell Reactivation ◽  
Group D

Fusion between HeLa and fibroblasts from complementation group D xeroderma pigmentosum (XPD) followed by challenge with small doses of ultraviolet light (u.v.) results in the production of hybrid cells expressing either HeLa (HD1) or XPD-like (HD2) sensitivity to u.v. and related repair capacity. Assays used included unscheduled DNA synthesis (UDS), DNA break accumulation in the presence of inhibitors of DNA repair synthesis and host cell reactivation of irradiated adenovirus. Complementation assay in heterokaryons reveals limited ability of HD2 to restore UDS in XPD nuclei. We believe this complementation is more apparent than real since proliferating hybrids of HD2 and XPD parentage are without exception u.v.-sensitive and express limited excision repair. On the other hand hybrids between HD2 and XPC, XPE or XPF fibroblasts show true complementation resulting in a return to normal u.v. sensitivity and elevated repair ability.

scholarly journals Interaction with OGG1 Is Required for Efficient Recruitment of XRCC1 to Base Excision Repair and Maintenance of Genetic Stability after Exposure to Oxidative Stress

2015 ◽  
Vol 35 (9) ◽  
pp. 1648-1658 ◽  
Author(s):  
Anna Campalans ◽  
Eva Moritz ◽  
Thierry Kortulewski ◽  
Denis Biard ◽  
Bernd Epe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Strand Break ◽  
Single Strand ◽  
Main Function ◽  
Single Strand Break ◽  
Single Strand Break Repair ◽  
Base Excision ◽  
Epidemiology Studies

XRCC1 is an essential protein required for the maintenance of genomic stability through its implication in DNA repair. The main function of XRCC1 is associated with its role in the single-strand break (SSB) and base excision repair (BER) pathways that share several enzymatic steps. We show here that the polymorphic XRCC1 variant R194W presents a defect in its interaction with the DNA glycosylase OGG1 after oxidative stress. While proficient for single-strand break repair (SSBR), this variant does not colocalize with OGG1, reflecting a defect in its involvement in BER. Consistent with a role of XRCC1 in the coordination of the BER pathway, induction of oxidative base damage in XRCC1-deficient cells complemented with the R194W variant results in increased genetic instability as revealed by the accumulation of micronuclei. These data identify a specific molecular role for the XRCC1-OGG1 interaction in BER and provide a model for the effects of the R194W variant identified in molecular cancer epidemiology studies.

scholarly journals Reduced DNA repair during differentiation of a myogenic cell line.

1976 ◽  
Vol 70 (3) ◽  
pp. 685-691 ◽  
Author(s):  
A C Chan ◽  
I G Walker
Keyword(s):  
Strand Break ◽  
Post Treatment ◽  
Single Strand ◽  
Repair Synthesis ◽  
Single Strand Break ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Before And After ◽  
Dna Strands ◽  
A Minor

Repair synthesis induced by 4-nitroquinoline-1-oxide (4NQO) in L6 myoblasts before and after cellular fusion was measured by [3H] thymidine incorporation into unreplicated DNA. The level of repair synthesis was reuced after the cells had fused into myotubes. The terminal addition of radioactive nucleotides into DNA strands occurred only to a minor extent, and the dilution of [3H] thymidine by intracellular nucleotide pools was shown not to be responsible for the observed difference in repair synthesis, Both the initial rate and the overall incorporation of [3H] thymidine were found to be 50% lower in the myotubes. 4NQO treatment of myoblasts and myotubes induced modifications in the DNA which were observed as single-strand breaks during alkaline sucrose sedimentation. After the myoblasts were allowed a post-treatment incubation, most of the single-strand breaks were not longer apparent. In contrast, a post-treatment incubation of myotubes did not change the extent of single-strand breakage seen. Both myoblasts and myotubes were equally effective in repairing single-strand breaks induced by X radiation. It would appear that when myoblasts fuse, a repair enzyme activity is lost, probably an endonuclease that recognizes one of the 4 NQO modifications of DNA. The result observed is a partial loss of repair synthetic ability and a complete loss of ability to remove the modification that appears as a single-strand break in alkali.

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