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RAD52 is required for RNA-templated recombination repair in post-mitotic neurons.

Publication ,  Journal Article
Welty, S; Teng, Y; Liang, Z; Zhao, W; Sanders, LH; Greenamyre, JT; Rubio, ME; Thathiah, A; Kodali, R; Wetzel, R; Levine, AS; Lan, L
Published in: J Biol Chem
January 26, 2018

It has been long assumed that post-mitotic neurons only utilize the error-prone non-homologous end-joining pathway to repair double-strand breaks (DSBs) associated with oxidative damage to DNA, given the inability of non-replicating neuronal DNA to utilize a sister chromatid template in the less error-prone homologous recombination (HR) repair pathway. However, we and others have found recently that active transcription triggers a replication-independent recombinational repair mechanism in G0/G1 phase of the cell cycle. Here we observed that the HR repair protein RAD52 is recruited to sites of DNA DSBs in terminally differentiated, post-mitotic neurons. This recruitment is dependent on the presence of a nascent mRNA generated during active transcription, providing evidence that an RNA-templated HR repair mechanism exists in non-dividing, terminally differentiated neurons. This recruitment of RAD52 in neurons is decreased by transcription inhibition. Importantly, we found that high concentrations of amyloid β, a toxic protein associated with Alzheimer's disease, inhibits the expression and DNA damage response of RAD52, potentially leading to a defect in the error-free, RNA-templated HR repair mechanism. This study shows a novel RNA-dependent repair mechanism of DSBs in post-mitotic neurons and demonstrates that defects in this pathway may contribute to neuronal genomic instability and consequent neurodegenerative phenotypes such as those seen in Alzheimer's disease.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

January 26, 2018

Volume

293

Issue

4

Start / End Page

1353 / 1362

Location

United States

Related Subject Headings

  • Resting Phase, Cell Cycle
  • Recombination, Genetic
  • Rats
  • Rad52 DNA Repair and Recombination Protein
  • RNA
  • Neurons
  • Mitosis
  • G1 Phase
  • DNA Breaks, Double-Stranded
  • Biochemistry & Molecular Biology
 

Citation

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Welty, S., Teng, Y., Liang, Z., Zhao, W., Sanders, L. H., Greenamyre, J. T., … Lan, L. (2018). RAD52 is required for RNA-templated recombination repair in post-mitotic neurons. J Biol Chem, 293(4), 1353–1362. https://doi.org/10.1074/jbc.M117.808402
Welty, Starr, Yaqun Teng, Zhuobin Liang, Weixing Zhao, Laurie H. Sanders, J Timothy Greenamyre, Maria Eulalia Rubio, et al. “RAD52 is required for RNA-templated recombination repair in post-mitotic neurons.J Biol Chem 293, no. 4 (January 26, 2018): 1353–62. https://doi.org/10.1074/jbc.M117.808402.
Welty S, Teng Y, Liang Z, Zhao W, Sanders LH, Greenamyre JT, et al. RAD52 is required for RNA-templated recombination repair in post-mitotic neurons. J Biol Chem. 2018 Jan 26;293(4):1353–62.
Welty, Starr, et al. “RAD52 is required for RNA-templated recombination repair in post-mitotic neurons.J Biol Chem, vol. 293, no. 4, Jan. 2018, pp. 1353–62. Pubmed, doi:10.1074/jbc.M117.808402.
Welty S, Teng Y, Liang Z, Zhao W, Sanders LH, Greenamyre JT, Rubio ME, Thathiah A, Kodali R, Wetzel R, Levine AS, Lan L. RAD52 is required for RNA-templated recombination repair in post-mitotic neurons. J Biol Chem. 2018 Jan 26;293(4):1353–1362.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

January 26, 2018

Volume

293

Issue

4

Start / End Page

1353 / 1362

Location

United States

Related Subject Headings

  • Resting Phase, Cell Cycle
  • Recombination, Genetic
  • Rats
  • Rad52 DNA Repair and Recombination Protein
  • RNA
  • Neurons
  • Mitosis
  • G1 Phase
  • DNA Breaks, Double-Stranded
  • Biochemistry & Molecular Biology