scholarly journals Quantitation of intracellular NAD(P)H can monitor an imbalance of DNA single strand break repair in base excision repair deficient cells in real time

2003 ◽  
Vol 31 (17) ◽  
pp. 104e-104 ◽  
Author(s):  
J. Nakamura
Keyword(s):  
Real Time ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
Single Strand Break Repair ◽  
Break Repair ◽  
Base Excision

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 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 Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1493 ◽  
Author(s):  
Kohl ◽  
Flach ◽  
Naumann ◽  
Brendel ◽  
Kleiner ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Donor Cell ◽  
Strand Break ◽  
Low Doses ◽  
Single Strand Break ◽  
Single Strand Break Repair ◽  
Myeloid Leukemias ◽  
Base Excision

Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and base excision repair, respectively. Here, we investigated the cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34− AML cell samples (n = 18) in comparison to healthy CD34+ donor cell samples (n = 8). Strikingly, talazoparib and APE1 inhibitor III demonstrated critical antileukemic efficacy in selected MDS/CMML and AML cell samples. Low doses of talazoparib and APE1 inhibitor III further increased the cytotoxic efficacy of decitabine in MDS/CMML and AML cells. Moreover, low doses of APE1 inhibitor III increased the cytotoxic efficacy of talazoparib in MDS/CMML and AML cells. In summary, talazoparib and APE1 inhibitor III demonstrated substantial antileukemic efficacy as single agents, in combination with decitabine, and combined with each other. Hence, our findings support further investigation of these agents in sophisticated clinical trials.

CK2 phosphorylation of XRCC1 facilitates dissociation from DNA and single-strand break formation during base excision repair

DNA Repair ◽  
2011 ◽  
Vol 10 (9) ◽  
pp. 961-969 ◽  
Author(s):  
Cecilia E. Ström ◽  
Oliver Mortusewicz ◽  
David Finch ◽  
Jason L. Parsons ◽  
Anne Lagerqvist ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
Base Excision ◽  
Break Formation
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