Role of yeast Rad5 and its human orthologs, HLTF and SHPRH in DNA damage tolerance.
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.
Unk
Ildiko
I
Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Temesvari krt.62, H-6726, Hungary.
Hajdú
Ildikó
I
Blastyák
András
A
Haracska
Lajos
L
D000818:Animals; D004249:DNA Damage; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*
D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C516226:SHPRH protein, human; D044767:Ubiquitin-Protein Ligases; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases