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

• Published in: DNA repair Vol. 9; no. 3; pp. 257 - 267
• Main Authors: Unk, Ildiko, Hajdú, Ildikó, Blastyák, András, Haracska, Lajos
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 02.03.2010
• Subjects: Animals; Damage bypass; DNA Damage; DNA Helicases - chemistry; DNA Helicases - metabolism; DNA polymerase; DNA Replication; DNA translocase; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Humans; Replication; Saccharomyces cerevisiae; Saccharomyces cerevisiae - chemistry; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; SWI/SNF2; Transcription Factors - chemistry; Transcription Factors - metabolism; Ubiquitin; Ubiquitin-Protein Ligases - chemistry; Ubiquitin-Protein Ligases - metabolism; Ubiquitin; Damage bypass; Replication; DNA polymerase; DNA translocase; SWI/SNF2
• ISSN: 1568-7864; 1568-7856
• DOI: 10.1016/j.dnarep.2009.12.013

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.