scholarly journals Faculty Opinions recommendation of Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis.

2021 ◽  
Author(s):  
Olga Lavrik
Keyword(s):  
Protein Complex ◽  
Temporal Dynamics ◽  
Strand Break ◽  
Single Strand ◽  
Complex Assembly ◽  
Single Strand Break ◽  
Single Strand Break Repair ◽  
Repair Protein ◽  
Base Excision ◽  
Protein Complex Assembly

scholarly journals Temporal dynamics of base excision / single-strand break repair protein complex assembly and disassembly are modulated by the PARP1/NAD+/SIRT6 axis

2021 ◽  
Author(s):  
Christopher A. Koczor ◽  
Kate M. Saville ◽  
Joel F. Andrews ◽  
Jennifer Clark ◽  
Qingming Fang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Temporal Dynamics ◽  
Excision Repair ◽  
Protein Complexes ◽  
Strand Break ◽  
Complex Assembly ◽  
Single Strand Break ◽  
Repair Protein ◽  
Base Excision

SUMMARYAssembly and disassembly of DNA repair protein complexes at sites of DNA damage is essential to maintain genomic integrity. We investigated factors coordinating assembly of the base excision repair (BER) proteins, DNA polymerase β (Polβ) and XRCC1, to DNA lesion sites, identifying a new role for Polβ in regulating XRCC1 disassembly from DNA repair complexes and conversely, demonstrating Polβ’s dependence on XRCC1 for complex assembly. RealPAR, a genetically-encoded probe for live cell imaging of poly(ADP-ribose) (PAR), reveals that Polβ and XRCC1 require PAR for repair complex assembly and PAR degradation for disassembly. We find that BER complex assembly is further modulated by attenuation / augmentation of NAD+ biosynthesis. Finally, SIRT6 does not regulate PARP1 activation but impairs XRCC1 recruitment, leading to diminished Polβ abundance at sites of DNA damage. These findings highlight coordinated yet independent roles for both PARP1 and SIRT6 and their regulation by NAD+ bioavailability to facilitate BER.

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.

End-damage-specific proteins facilitate recruitment or stability of X-ray cross-complementing protein 1 at the sites of DNA single-strand break repair

FEBS Journal ◽  
2005 ◽  
Vol 272 (22) ◽  
pp. 5753-5763 ◽  
Author(s):  
Jason L. Parsons ◽  
Irina I. Dianova ◽  
Emma Boswell ◽  
Michael Weinfeld ◽  
Grigory L. Dianov
Keyword(s):  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
X Ray ◽  
Single Strand Break Repair ◽  
Specific Proteins ◽  
Break Repair

Motor Coordination in Space: An Analysis of the Effects of Microgravity on XRCCI DNA Repair Protein Function

2020 ◽  
Author(s):  
Vishruth Nagam
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Protein Function ◽  
Motor Coordination ◽  
Strand Break ◽  
Single Strand Break ◽  
Single Strand Break Repair ◽  
Repair Protein ◽  
Mature Neurons ◽  
Microgravity Conditions

Abstract While in space, astronauts have been known to face exposure to stressors that may increase susceptibility to DNA damage. If DNA repair proteins are defective or nonexistent, DNA mutations may accumulate, causing increasingly abnormal function as one ages [1]. The DNA single-strand break repair protein XRCC1 is important for cerebellar neurogenesis and interneuron development [2]. According to previous studies, a deficiency of XRCC1 can lead to an increase in DNA damage, in mature neurons, and ataxia (a progressive loss of motor coordination) [2]. I propose to address how XRCC1’s efficiency can change in microgravity conditions. This experiment’s relevance is underscored by the importance of motor coordination and physical fitness for astronauts; determining the potential effects of microgravity on XRCC1 is crucial for future space exploration.

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