4.7 Review

Transcription and DNA Damage: Holding Hands or Crossing Swords?

Journal

JOURNAL OF MOLECULAR BIOLOGY
Volume 429, Issue 21, Pages 3215-3229

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2016.11.002

Keywords

DNA damage response (DDR); R loops; RNA binding proteins (RBPs); Non-coding RNAs (ncRNAs)

Funding

  1. Fondazione Italiana Ricerca Sul Cancro (FIRC) [15050]
  2. Associazione Italiana per la Ricerca sul Cancro, AIRC [12971]
  3. Human Frontier Science Program [RGP 0014/2012]
  4. Cariplo Foundation [2010.0818]
  5. Marie Curie Initial Training Networks [PEOPLE ITN (CodAge)]
  6. Fondazione Telethon [GGP12059]
  7. Association for International Cancer Research (AICR)
  8. Progetti di Ricerca di Interesse Nazionale (PRIN)
  9. Italian Ministry of Education Universities and Research EPIGEN Project
  10. European Research Council [322726]
  11. European Research Council (ERC) [322726] Funding Source: European Research Council (ERC)

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Transcription has classically been considered a potential threat to genome integrity. Collision between transcription and DNA replication machinery, and retention of DNA:RNA hybrids, may result in genome instability. On the other hand, it has been proposed that active genes repair faster and preferentially via homologous recombination. Moreover, while canonical transcription is inhibited in the proximity of DNA double-strand breaks, a growing body of evidence supports active non-canonical transcription at DNA damage sites. Small non-coding RNAs accumulate at DNA double-strand break sites in mammals and other organisms, and are involved in DNA damage signaling and repair. Furthermore, RNA binding proteins are recruited to DNA damage sites and participate in the DNA damage response. Here, we discuss the impact of transcription on genome stability, the role of RNA binding proteins at DNA damage sites, and the function of small non-coding RNAs generated upon damage in the signaling and repair of DNA lesions. (C) 2016 Elsevier Ltd. All rights reserved.

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