Analyses of the interaction of WRNIP1 with Werner syndrome protein (WRN) in vitro and in the cell

Kawabe, Yoh-ichi; Seki, Masayuki; Yoshimura, Akari; Nishino, Katsuaki; Hayashi, Tomoko; Takeuchi, Takashi; Iguchi, Sohta; Kusa, Yumiko; Ohtsuki, Makoto; Tsuyama, Takashi; Imamura, Osamu; Matsumoto, Takehisa; Furuichi, Yasuhiro; Tada, Shusuke; Enomoto, Takemi

doi:10.1016/j.dnarep.2006.04.006

Cited by 36 publications

(48 citation statements)

References 26 publications

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“…18) However, the biochemical interactions between WRNIP1 and WRN shown in the present study suggest that WRNIP1 and WRN act together under certain conditions. This possibility is not necessarily incompatible with genetic data obtained from budding yeast and DT40 cells.…”

Section: Discussioncontrasting

confidence: 38%

“…WRNIP1 Stimulates Binding of WRN to TemplatePrimer DNA Although binding of WRNIP1 to WRN has been demonstrated in vitro and in the cell, 10,18) it is not clear how WRNIP1 biochemically affects the function of WRN. Therefore, studies were performed to determine if WRNIP1 affects binding of WRN to template-primer DNA.…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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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Section: Discussioncontrasting

confidence: 38%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…Wrnip1 Oligomerization via Its C Terminus Contributes to Foci Localization-It has been shown previously that Wrnip1 forms homo-oligomers (11) and that its Ub-binding zinc finger may be involved in this process (34). Similarly, it has been demonstrated that Rad18 can dimerize (35) and that its UBZ domain is indispensable for this phenomenon (36).…”

Section: Wrnip1 Is Concentrated In Replication Factories and Othermentioning

confidence: 99%

Human Wrnip1 Is Localized in Replication Factories in a Ubiquitin-binding Zinc Finger-dependent Manner

Crosetto

Bienko

Hibbert

et al. 2008

Journal of Biological Chemistry

102

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Wrnip1 (Werner helicase-interacting protein 1) has been implicated in the bypass of stalled replication forks in bakers' yeast. However, the function(s) of human Wrnip1 has remained elusive so far. Here we report that Wrnip1 is distributed inside heterogeneous structures detectable in nondamaged cells throughout the cell cycle. In an attempt to characterize these structures, we found that Wrnip1 resides in DNA replication factories. Upon treatments that stall replication forks, such as UVC light, the amount of chromatin-bound Wrnip1 and the number of foci significantly increase, further implicating Wrnip1 in DNA replication. Interestingly, the nuclear pattern of Wrnip1 appears to extend to a broader landscape, as it can be detected in promyelocytic leukemia nuclear bodies. The presence of Wrnip1 into these heterogeneous subnuclear structures requires its ubiquitin-binding zinc finger (UBZ) domain, which is able to interact with different ubiquitin (Ub) signals, including mono-Ub and chains linked via lysine 48 and 63. Moreover, the oligomerization of Wrnip1 mediated by its C terminus is also important for proper subnuclear localization. Our study is the first to reveal the composite and regulated topography of Wrnip1 in the human nucleus, highlighting its potential role in replication and other nuclear transactions.

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“…32 The gene responsible for the progeria disease, Werner Syndrome, encodes WRN, which is a member of the RecQ family of DNA helicases with an additional exonuclease activity. WHIP has multiple binding partners [32][33][34][35][36][37][38] and WRN also binds replication protein A, PCNA, DNA topoisomerase I and DNA polymerase. [39][40][41][42] The amino acid sequence of WHIP is similar to that of the replication factor C (RFC) family of clamp loader proteins but also contains a Walker A & B motif for ATPase activity (Fig.…”

Section: Introductionmentioning

confidence: 99%

The discovery of a Werner helicase interacting protein (WHIP) association with the nuclear pore complex

Kaur¹,

White²,

DiGuilio³

et al. 2010

Cell Cycle

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Analyses of the interaction of WRNIP1 with Werner syndrome protein (WRN) in vitro and in the cell

Cited by 36 publications

References 26 publications

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

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

Human Wrnip1 Is Localized in Replication Factories in a Ubiquitin-binding Zinc Finger-dependent Manner

The discovery of a Werner helicase interacting protein (WHIP) association with the nuclear pore complex

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