The product of Saccharomyces cerevisiae WHIP/MGS1, a gene related to replication factor C genes, interacts functionally with DNA polymerase δ

Branzei, Dana; Seki, Masayuki; Onoda, Fumitoshi; Enomoto, Takemi

doi:10.1007/s00438-002-0757-3

Cited by 53 publications

(81 citation statements)

References 49 publications

(61 reference statements)

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“…When PCNA is polyubiquitinated in this manner, it promotes damage bypass through template-switching (Zhang and Lawrence, 2005;Torres-Ramos et al, 2002;Blastyak et al, 2007). Interestingly, deletion of RAD18 or MMS2 suppresses the growth defect of Polδ mutants, and a similar phenomenon was observed after deleting MGS1 (Branzei et al, 2002b). Moreover, mgs1 mutation suppresses the growth defect of a Polδ mutant caused by expression of E. coli RuvC, a bacterial Holliday junction resolvase, suggesting that Mgs1 generates a Holliday junction-like structure that may be formed in the process of the template-switch type of damage bypass (Hishida et al, 2002).…”

Section: Introductionmentioning

confidence: 83%

“…On the other hand, genetic evidences obtained from analyses of budding yeast mutants indicate that Mgs1 may function in a DNA damage tolerance pathway that is similar to, but distinct from, the pathway involving Rad6, Rad18, Rad5, Mms2, and Ubc13, and has been postulated to be a template-switch type of damage avoidance pathway (Hishida et al, 2002;Branzei et al, 2002bBranzei et al, , 2004. Very recently, biochemical evidences supporting a Rad18-and Rad5-driven template-switch at stalled forks was reported (Branzei et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Overproduction of Mgs1 is lethal or very toxic in combination with mutations in genes that encode proteins involved in DNA replication, such as DNA polymerase δ (Polδ), RFC, PCNA, and RPA (Branzei et al, 2002b). Mgs1 physically and functionally interacts in vivo with budding yeast Pol31, the second subunit of Polδ (Vijeh Motlagh et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Physical and functional interaction between WRNIP1 and RAD18

et al. 2009

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WRN interacting protein 1 (WRNIP1) was originally identified as a protein that interacts with the Werner syndrome responsible gene product (WRN). WRNIP1 is a highly conserved protein from E. coli to humans. Genetic studies in budding yeast suggested that the yeast orthlog of WRNIP1, Mgs1, may function in a DNA damage tolerance pathway that is similar to, but distinct from, the templateswitch damage avoidance pathway involving Rad6, Rad18, Rad5, Mms2, and Ubc13. Here we report that human WRNIP1 binds in an ATP dependent manner to both forked DNA that mimics stalled replication forks and to template/primer DNA. We found that WRNIP1 interacts physically with RAD18 and interferes with the binding of RAD18 to forked DNA and to template/primer DNA. In contrast, RAD18 enhances the binding of WRNIP1 to these DNAs, suggesting that WRNIP1 targets DNA bound by RAD18.

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Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Physical and functional interaction between WRNIP1 and RAD18

et al. 2009

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“…nation intermediates. Previous studies of Mgs1 suggested that its function is somehow related to the function of DNA polymerase δ (Polδ), which is required for cellular DNA replication (Hishida et al, 2002;Branzei et al, 2002b). In this context, we have observed stimulation of Polδ activity by WRNIP1 at the initiation stage in vitro (Tsurimoto et al, 2005).…”

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confidence: 55%

Vertebrate WRNIP1 and BLM are required for efficient maintenance of genome stability

et al. 2008

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Bloom syndrome (BS) is rare autosomal recessive disorder associated with chromosomal instability. The gene responsible for BS, BLM, encodes a protein belonging to the RecQ helicase family. Disruptions of the SGS1 gene of Saccharomyces cerevisiae, which encodes the RecQ helicase homologue in the budding yeast, causes accelerated aging, and this phenotype is enhanced by the disruption of MGS1, the budding yeast homologue for WRNIP1. To examine the functional relationship between RecQ and WRNIP1 in vertebrate cells, we generated and characterized wrnip1/blm cells derived from the chicken B-lymphocyte line DT40. wrnip1/blm cells showed an additive elevation of sister chromatid exchange (SCE), suggesting that both genes independently contribute to the suppression of excess SCE formation. The double mutants were more sensitive to DNA damage from camptothecin (CPT), but not to damage from methyl methanesulfonate, than either single mutant. This result suggests that WRNIP1 and BLM function independently to repair DNA or induce tolerance to the lesions induced by CPT.

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“…12) In addition, overproduction of Mgs1p is lethal or very toxic when it is combined with mutations in the genes that encode proteins involved in DNA replication, such as replication protein A, replication factor C, proliferating cell nuclear antigen and DNA polymerase d (Pold). 13) Mgs1p physically and functionally interacts in vivo with budding yeast Pol31, the second subunit of Pold. 14) Human WRNIP1 also interacts directly with human Pold and stimulates the DNA synthesizing activity of Pold by increasing initiation frequency of DNA synthesis from primers annealed on template DNA (template-primer DNA).…”

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confidence: 99%

Werner Interacting Protein 1 Promotes Binding of Werner Protein to Template-Primer DNA

Kanamori

Seki

Yoshimura

et al. 2011

Biological & Pharmaceutical Bulletin

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Werner syndrome (WS) is a rare autosomal recessive disorder that displays many of the clinical symptoms of normal aging at an early age. From the second decade of life onward, WS patients develop pathologies that resemble many of the traits of normal aging, such as osteoporosis, ocular cataracts, graying and loss of hair, diabetes mellitus, arteriosclerosis, and cancer. 1) WS is caused by mutation of a single gene that encodes a 1432-amino acid protein (WRN).2) WRN possesses multiple enzyme activities, including DNA-dependent ATPase, exonuclease, and DNA helicase activities. [3][4][5] Somatic cells derived from WS patients display subtle replication defects, genomic instability, and altered telomere dynamics, suggesting an important role of WRN in DNA metabolic pathways. [6][7][8][9] This is consistent with observations that a variety of proteins that interact with WRN are involved in DNA replication, repair, recombination, transcription, and maintenance of telomere structure.3) We identified a new protein that interacts with WRN and designated it originally Werner Helicase Interacting Protein (WHIP) 10) and renamed it later as WRN interacting protein 1 (WRNIP1). WRNIP1 belongs to the AAAϩ class of the ATPase family and is conserved from Escherichia (E.) coli to human. 10)Mutation in the gene encoding the budding yeast ortholog of WRNIP1, maintenance of genome stability 1 (MGS1) causes hyper recombination and early aging in yeast cells. 10,11) Genetic analyses using MGS1 mutants revealed that Mgs1p is required to prevent genome instability caused by replication arrest and is not involved in the repair of DNA lesions.12) In addition, overproduction of Mgs1p is lethal or very toxic when it is combined with mutations in the genes that encode proteins involved in DNA replication, such as replication protein A, replication factor C, proliferating cell nuclear antigen and DNA polymerase d (Pold). 13)Mgs1p physically and functionally interacts in vivo with budding yeast Pol31, the second subunit of Pold.14) Human WRNIP1 also interacts directly with human Pold and stimulates the DNA synthesizing activity of Pold by increasing initiation frequency of DNA synthesis from primers annealed on template DNA (template-primer DNA).15) In this context, it is of note that WRN interacts with Pold 16) and stimulates the DNA synthesizing activity of Pold by increasing the length of synthesized DNA.17) Since WRNIP1 interacts with WRN, 10,18) WRNIP1 and WRN may interact with templateprimer DNA in a cooperative fashion to regulate the activity of Pold. However, the biochemical relationships between WRNIP1 and WRN at the template-primer DNA remain elusive.In this study, the biochemical relationships between purified WRNIP1 and WRN on template-primer DNA were analyzed. MATERIALS AND METHODS Protein PreparationPreparation of baculovirus for the expression of human WRNIP1 was described previously. 15)High-5 cells infected with recombinant virus encoding FLAG-WRNIP1 were cultured for 3 d and collected by centrifugation. Cells were lysed with...

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The product of Saccharomyces cerevisiae WHIP/MGS1, a gene related to replication factor C genes, interacts functionally with DNA polymerase δ

Cited by 53 publications

References 49 publications

Physical and functional interaction between WRNIP1 and RAD18

Physical and functional interaction between WRNIP1 and RAD18

Vertebrate WRNIP1 and BLM are required for efficient maintenance of genome stability

Werner Interacting Protein 1 Promotes Binding of Werner Protein to Template-Primer DNA

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