Deficiency of the Caenorhabditis elegans DNA Polymerase .ETA. Homologue Increases Sensitivity to UV Radiation during Germ-line Development

Ohkumo, Tsuyoshi; Masutani, Chikahide; Eki, Toshihiko; Hanaoka, Fumio

doi:10.1247/csf.31.29

Cited by 23 publications

(24 citation statements)

References 47 publications

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“…Polη-1 was amplified by RT-PCR and cloned into pGBKT7. Two spliced products were detected, one with a 57 bp deletion in exon 7, as previously reported [19]. Both products were assayed.…”

Section: Pair-wise Yeast Two-hybrid Assays and Interaction Domain Mapsupporting

confidence: 52%

Comparative analysis of in vivo interactions between Rev1 protein and other Y-family DNA polymerases in animals and yeasts

et al. 2008

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SummaryEukaryotes are endowed with multiple specialized DNA polymerases, some (if not all) of which are believed to play important roles in the tolerance of base damage during DNA replication. Among these DNA polymerases, Rev1 protein (a deoxycytidyl transferase) from vertebrates interacts with several other specialized polymerases via a highly conserved C-terminal region. The present studies assessed whether these interactions are retained in more experimentally tractable model systems, including yeasts, flies, and the nematode C. elegans. We observed a physical interaction between Rev1 protein and other Y-family polymerases in the fruit fly Drosophila melanogaster. However, despite the fact that the C-terminal region of Drosophila and yeast Rev1 are conserved from vertebrates to a similar extent, such interactions were not observed in S. cerevisiae or S. pombe. With respect to regions in specialized DNA polymerases that are required for interaction with Rev1, we find predicted disorder to be an underlying structural commonality. The results of this study suggest that special consideration should be exercised when making mechanistic extrapolations regarding translesion DNA synthesis from one eukaryotic system to another.

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“…Polη-1 was amplified by RT-PCR and cloned into pGBKT7. Two spliced products were detected, one with a 57 bp deletion in exon 7, as previously reported [19]. Both products were assayed.…”

Section: Pair-wise Yeast Two-hybrid Assays and Interaction Domain Mapsupporting

confidence: 52%

Comparative analysis of in vivo interactions between Rev1 protein and other Y-family DNA polymerases in animals and yeasts

et al. 2008

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“…Germline knockdown of the dPolη homolog, polh-1, in C. elegans caused increased sensitivity of early embryos to UV irradiation, suggesting that POLH-1 is required for genome maintenance during embryogenesis (Ohkumo et al, 2006). POLH-1 has been further proposed to prevent stalling of replication forks during early embryogenesis by replacing the replicative polymerase on chromatin to quickly bypass DNA lesions (Holway et al, 2006;Kim and Michael, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…dPolη larvae exhibit increased sensitivity to UV irradiation, and homologous recombination is impaired in dPolη flies (Kane et al, 2012). Germline knockdown of polh-1, the C. elegans Polη homolog, causes increased sensitivity of early embryos to UV irradiation (Ohkumo et al, 2006). Recent studies suggest that POLH-1 functions in C. elegans to keep the rapid cell cycles of early embryogenesis on schedule (Holway et al, 2006;Kim and Michael, 2008).…”

Section: Introductionmentioning

confidence: 99%

TRIP/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase η

Wallace

Merkle

et al. 2014

Development

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We previously identified a Drosophila maternal effect-lethal mutant named 'no poles' (nopo). Embryos from nopo females undergo mitotic arrest with barrel-shaped, acentrosomal spindles during the rapid cycles of syncytial embryogenesis because of activation of a Chk2-mediated DNA checkpoint. NOPO is the Drosophila homolog of human TNF receptor associated factor (TRAF)-interacting protein (TRIP), which has been implicated in TNF signaling. NOPO and TRIP contain RING domains closely resembling those of known E3 ubiquitin ligases. We herein sought to elucidate the mechanism by which TRIP/NOPO promotes genomic stability by performing a yeast two-hybrid screen to identify potential substrates/interactors. We identified members of the Y-family of DNA polymerases that facilitate replicative bypass of damaged DNA (translesion synthesis) as TRIP interactors. We show that TRIP and NOPO co-immunoprecipitate with human and Drosophila Polη, respectively, from cultured cells. We generated a null mutation in Drosophila Polη (dPolη) and found that dPolη-derived embryos have increased sensitivity to ultraviolet irradiation and exhibit nopo-like mitotic spindle defects. dPolη and nopo interact genetically in that overexpression of dPolη in hypomorphic nopo-derived embryos suppresses nopo phenotypes. We observed enhanced ubiquitylation of Polη by TRIP and NOPO E3 ligases in human cells and Drosophila embryos, respectively, and show that TRIP promotes hPolη localization to nuclear foci in human cells. We present a model in which TRIP/NOPO ubiquitylates Polη to positively regulate its activity in translesion synthesis.

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“…[Larimer et al, 1989;Pothof et al, 2003;Takeuchi et al, 2004;Aslett and Wood, 2006] pol zeta ? [Misra and Vos, 1993;McDonald et al, 1997;Tanaka et al, 2000;Ohkumo et al, 2006] pol theta…”

Section: General Strategies For Dna Interstrand Crosslink Repair In Bmentioning

confidence: 99%

Strategies for DNA interstrand crosslink repair: Insights from worms, flies, frogs, and slime molds

McVey

2010

Environ and Mol Mutagen

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DNA interstrand crosslinks (ICLs) are complex lesions that covalently link both strands of the DNA double helix and impede essential cellular processes such as DNA replication and transcription. Recent studies suggest that multiple repair pathways are involved in their removal. Elegant genetic analysis has demonstrated that at least three distinct sets of pathways cooperate in the repair and/or bypass of ICLs in budding yeast. Although the mechanisms of ICL repair in mammals appear similar to those in yeast, important differences have been documented. In addition, mammalian crosslink repair requires other repair factors, such as the Fanconi anemia proteins, whose functions are poorly understood. Because many of these proteins are conserved in simpler metazoans, nonmammalian models have become attractive systems for studying the function(s) of key crosslink repair factors. This review discusses the contributions that various model organisms have made to the field of ICL repair. Specifically, it highlights how studies performed with C. elegans, Drosophila, Xenopus, and the social amoeba Dictyostelium serve to complement those from bacteria, yeast, and mammals. Together, these investigations have revealed that although the underlying themes of ICL repair are largely conserved, the complement of DNA repair proteins utilized and the ways in which each of the proteins is used can vary substantially between different organisms.

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Deficiency of the Caenorhabditis elegans DNA Polymerase .ETA. Homologue Increases Sensitivity to UV Radiation during Germ-line Development

Cited by 23 publications

References 47 publications

Comparative analysis of in vivo interactions between Rev1 protein and other Y-family DNA polymerases in animals and yeasts

Comparative analysis of in vivo interactions between Rev1 protein and other Y-family DNA polymerases in animals and yeasts

TRIP/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase η

Strategies for DNA interstrand crosslink repair: Insights from worms, flies, frogs, and slime molds

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