Regulation of DNA damage response by RNA/DNA-binding proteins: Implications for neurological disorders and aging

Kodavati, Manohar; Maloji Rao, Vikas H.; Provasek, Vincent E.; Hegde, Muralidhar L.

doi:10.1016/j.arr.2024.102413

Ageing Research Reviews

2024

DOI: 10.1016/j.arr.2024.102413

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Regulation of DNA damage response by RNA/DNA-binding proteins: Implications for neurological disorders and aging

Manohar Kodavati,

Vikas H. Maloji Rao,

Vincent E. Provasek

et al.

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Cited by 3 publications

References 203 publications

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Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin

Spencer,

Berntsson,

Buguet

et al. 2025

Journal of the Neurological Sciences

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Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin

Spencer,

Berntsson,

Buguet

et al. 2025

Journal of the Neurological Sciences

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A Commentary on Mitochondrial Dysfunction and Compromised DNA Repair in Neurodegeneration: The Emerging Role of FUS in ALS

Kodavati,

Hegde

2024

J Exp Neurosci

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Mitochondrial dysfunction plays a pivotal role in the progression of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s, and Parkinson’s disease. Recent discoveries have highlighted the involvement of DNA damage and repair processes, particularly mitochondrial DNA (mtDNA) damage, in these conditions. This commentary reflects on our recent findings, demonstrating the RNA/DNA binding protein fused in sarcoma (FUS)’s crucial role in maintaining mtDNA integrity through interactions with mitochondrial DNA ligase IIIα (mtLig3). Our studies provide direct evidence of increased mtDNA damage in ALS-linked FUS mutant cells, emphasizing the potential of targeting DNA repair pathways to mitigate neurodegeneration. Furthermore, the restoration of mitochondrial function through targeted expression of human DNA ligase 1 (Lig1) in FUS mutant models showcases the therapeutic promise of DNA repair mechanisms in neurodegenerative diseases. These insights offer new molecular understanding and open up future avenues for therapeutic interventions, particularly in FUS-associated ALS and related disorders.

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Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair

Khodyreva,

Dyrkheeva,

Lavrik

2024

Biomedicines

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The nervous system is susceptible to DNA damage and DNA repair defects, and if DNA damage is not repaired, neuronal cells can die, causing neurodegenerative diseases in humans. The overall picture of what is known about DNA repair mechanisms in the nervous system is still unclear. The current challenge is to use the accumulated knowledge of basic science on DNA repair to improve the treatment of neurodegenerative disorders. In this review, we summarize the current understanding of the function of DNA damage repair, in particular, the base excision repair and double-strand break repair pathways as being the most important in nervous system cells. We summarize recent data on the proteins involved in DNA repair associated with neurodegenerative diseases, with particular emphasis on PARP1 and ND-associated proteins, which are involved in DNA repair and have the ability to undergo liquid–liquid phase separation.

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Regulation of DNA damage response by RNA/DNA-binding proteins: Implications for neurological disorders and aging

Cited by 3 publications

References 203 publications

Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin

Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin

A Commentary on Mitochondrial Dysfunction and Compromised DNA Repair in Neurodegeneration: The Emerging Role of FUS in ALS

Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair

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