Role of yeast Rad5 and its human orthologs, HLTF and SHPRH in DNA damage tolerance

DNA Repair (Amst). 2010 Mar 2;9(3):257-67. doi: 10.1016/j.dnarep.2009.12.013. Epub 2010 Jan 21.

Abstract

In the yeast Saccharomyces cerevisiae, the Rad6-Rad18 DNA damage tolerance pathway constitutes a major defense system against replication fork blocking DNA lesions. The Rad6-Rad18 ubiquitin-conjugating/ligase complex governs error-free and error-prone translesion synthesis by specialized DNA polymerases, as well as an error-free Rad5-dependent postreplicative repair pathway. For facilitating replication through DNA lesions, translesion synthesis polymerases copy directly from the damaged template, while the Rad5-dependent damage tolerance pathway obtains information from the newly synthesized strand of the undamaged sister duplex. Although genetic data demonstrate the importance of the Rad5-dependent pathway in tolerating DNA damages, there has been little understanding of its mechanism. Also, the conservation of the yeast Rad5-dependent pathway in higher order eukaryotic cells remained uncertain for a long time. Here we summarize findings published in recent years regarding the role of Rad5 in promoting error-free replication of damaged DNA, and we also discuss results obtained with its human orthologs, HLTF and SHPRH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Damage*
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism*
  • DNA Replication
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • DNA-Binding Proteins
  • HLTF protein, human
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • SHPRH protein, human
  • Ubiquitin-Protein Ligases
  • RAD5 protein, S cerevisiae
  • DNA Helicases