Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain

Tanaka, Kiyoji; Miura, Naoyuki; Satokata, Ichiro; Miyamoto, Iwai; Yoshida, Michihiro C.; Satoh, Yoshiaki; Kondo, Seiji; Yasui, Akira; Okayama, Hiroto; Okada, Yoshio

doi:10.1038/348073a0

Cited by 368 publications

(159 citation statements)

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“…During NER, TFIIH is thought to be recruited to the damage site at an early step of the repair process (12)(13)(14). The initial recognition of DNA lesions is likely to involve a nucleoprotein⅐DNA complex consisting of XPA, a zinc finger protein with some specificity for UV-or chemical carcinogendamaged DNA (15)(16)(17)(18)(19), RPA (20 -24), and probably other factors. TFIIH may then be involved in the formation of a preincision complex through an interaction with the COOH terminus of XPA (25).…”

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confidence: 99%

DNA Damage Recognition by XPA Protein Promotes Efficient Recruitment of Transcription Factor II H

Nocentini¹,

Coin²,

Saijo³

et al. 1997

Journal of Biological Chemistry

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104

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The human basal transcription factor IIH (TFIIH) is an essential component of the nucleotide excision repair machinery. TFIIH is required for reaction steps concomitant with or prior to the formation of dual incisions in the damaged DNA strand. To understand the mechanism underlying the recruitment of TFIIH to DNA damage sites we have analyzed i) the direct affinity of TFIIH for damaged or undamaged DNA and ii) the interaction of TFIIH with XPA⅐DNA complexes, formed using unirradiated or UV-irradiated DNA.Filter binding assays showed that TFIIH has some affinity for the DNA, but in contrast to XPA, does not show any preference for UV-irradiated DNA. Pull-down experiments demonstrated that TFIIH binds to XPA⅐DNA complexes in an UV damage-dependent manner by a direct protein-protein interaction with XPA. We propose that an enhancement of the affinity of XPA protein for TFIIH could arise from conformational changes of XPA when it binds to UV lesions on the DNA.Transcription initiation of protein coding genes and nucleotide excision repair (NER) 1 of damaged DNA were shown to be connected through the dual action of TFIIH, a multisubunit protein complex that contains several enzymatic activities (reviewed in Refs. 1 and 2). Although the protein composition and the nature of the different subunits are almost completely determined (Ref. 3 and references therein), relatively little is known concerning the precise functions of TFIIH in both mechanisms. However, genetic studies in yeast (4, 5) and Chinese hamster ovary cells (6), as well as the association of mutations in XPB and XPD with the human disorders xeroderma pigmentosum (XP), Cockayne syndrome, and trichothiodystrophy (7, 1), demonstrate the crucial importance of TFIIH in cellular DNA metabolism.During transcription initiation, TFIIH is thought to be recruited to a promoter, after the formation of the preinitiation complex containing TFIID, TFIIB, TFIIF, and RNA polymerase II on the TATA box consensus sequence (8). Once associated with this complex, TFIIH is likely to function through its ATPdependent helicase subunits, which may facilitate the opening of the promoter region (9) to allow the reading of the DNA. The cyclin dependent-kinase activity of TFIIH phosphorylates the carboxyl-terminal domain of RNA polymerase II in a reaction that has been proposed to activate the elongation process (10, 11). During NER, TFIIH is thought to be recruited to the damage site at an early step of the repair process (12-14). The initial recognition of DNA lesions is likely to involve a nucleoprotein⅐DNA complex consisting of XPA, a zinc finger protein with some specificity for UV-or chemical carcinogendamaged DNA (15-19), RPA (20 -24), and probably other factors. TFIIH may then be involved in the formation of a preincision complex through an interaction with the COOH terminus of XPA (25). The precise role played by TFIIH during the early reaction steps of NER is not yet certain, but the ATP-dependent helicase activities of the 6) may facilitate the formation of an open DNA com...

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mentioning

confidence: 99%

DNA Damage Recognition by XPA Protein Promotes Efficient Recruitment of Transcription Factor II H

Nocentini¹,

Coin²,

Saijo³

et al. 1997

Journal of Biological Chemistry

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104

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“…Enhanced removal of LW-induced pyrimidine dimers lowers skin cancer rates in mice, indicating that unrepaired dimers cause cancer in mammalian skin (343). Individuals with the heritable syndrome Xeroderma pigmentosum (XP) have impaired ability to remove DNA lesions induced by UV and consequentially are extremely sensitive to UV exposure, which results in an increased risk of developing skin cancers (344)(345)(346)(347)(348)(349)(350)(351)(352)(353)(354)(355)(356)(357). Generation of mice deficient in XP genes have confirmed the important role these gene products play in protecting against UV-induced tumorigenesis (358)(359)(360) (362)(363)(364)(365)(366)(367)(368) [for review, see (369)].…”

Section: The Spindle Checkpointmentioning

confidence: 99%

Cell cycle control, checkpoint mechanisms, and genotoxic stress.

Shackelford

Kaufmann

Paules

1999

Environ Health Perspect

183

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The ability of cells to maintain genomic integrity is vital for cell survival and proliferation. Lack of fidelity in DNA replication and maintenance can result in deleterious mutations leading to cell death or, in multicellular organisms, cancer. The purpose of this review is to discuss the known signal transduction pathways that regulate cell cycle progression and the mechanisms cells employ to insure DNA stability in the face of genotoxic stress. In particular, we focus on mammalian cell cycle checkpoint functions, their role in maintaining DNA stability during the cell cycle following exposure to genotoxic agents, and the gene products that act in checkpoint function signal transduction cascades. Key transitions in the cell cycle are regulated by the activities of various protein kinase complexes composed of cyclin and cyclin-dependent kinase (Cdk) molecules. Surveillance control mechanisms that check to ensure proper completion of early events and cellular integrity before initiation of subsequent events in cell cycle progression are referred to as cell cycle checkpoints and can generate a transient delay that provides the cell more time to repair damage before progressing to the next phase of the cycle. A variety of cellular responses are elicited that function in checkpoint signaling to inhibit cyclin/Cdk activities. These responses include the p53-dependent and p53-independent induction of Cdk inhibitors and the p53-independent inhibitory phosphorylation of Cdk molecules themselves. Eliciting proper Gl, S, and G2 checkpoint responses to double-strand DNA breaks requires the function of the Ataxia telangiectasia mutated gene product. Several human heritable cancer-prone syndromes known to alter DNA stability have been found to have defects in checkpoint surveillance pathways. Exposures to several common sources of genotoxic stress, including oxidative stress, ionizing radiation, UV radiation, and the genotoxic compound benzo[alpyrene, elicit cell cycle checkpoint responses that show both similarities and differences in their molecular signaling. -Environ Health Perspect 107(Suppl 1):5-24 (1999 (Figure 1) (6,8).The description of the cell cycle being divided into four phases led to many questions about the regulatory mechanisms cells employ to ensure an ordered and sequential progression from G1 to M phase, as well as the mechanisms ensuring DNA stability. Some of these questions were summarized as the "completion" and "alternation" problems (8,9). In the completion problem, the question is raised as to how cells ensure that specific events are completed before subsequent events are initiated. For example, cells must ensure that once DNA is condensed for segregation during cytokinesis, it remains condensed throughout M phase and does not prematurely decondense. In the alternation problem, the question is raised as to how cells ensure that once an event is completed, it is not inappropriately repeated. For example, cells must ensure that once DNA replication in S phase is completed, it is followed by DNA co...

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“…However, recent studies (Guzder et al, 1995) have shown that the RAD14 gene contains an intron and the Rad14 protein actually contains 371 amino acid residues and has a molecular weight of 43 kDa. The amino acid sequence homology identifies the Rad14 protein as the human xeroderma pigmentosum (XPA) homologue, as does the existence of a putative CX 2 CX 18 CX 2 C zinc finger DNA binding motif (Tanaka et al, 1990;Bankmann et al, 1992): this motif is present in other eukaryotic XPA homologues which have been identified (Shimamoto et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Characterization of therad14-2 Mutant ofSaccharomyces cerevisiae: Implications for the Recognition of UV Photoproducts by the Rad14 Protein

Jones

Reed

Waters

1997

Yeast

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The RAD14 gene of Saccharomyces cerevisiae is required for the incision step of the nucleotide excision repair process. The Rad14 protein can bind zinc, possesses a potential zinc finger DNA binding domain and has been shown to bind specifically to damaged DNA. Differences in UV sensitivity exist between a rad14 deletion strain and a putative rad14 point mutant, the point mutant being more resistant to UV than the deletion strain. Here, we confirm that the rad14 deletion strain repairs neither UV‐induced cyclobutane pyrimidine dimers (CPDs) nor endonuclease III‐sensitive damage sites, whereas the point mutant cannot repair the former but can repair the latter. From this it can be inferred that the point mutant produces an altered protein product allowing recognition of endonuclease III sensitive sites but not CPDs. To investigate this, the rad14 mutant allele was sequenced. It contained two GC‐AT transition mutations when compared to the wild‐type RAD14 gene sequence. When the rad14 point mutant sequence is translated, alterations within the putative zinc finger binding domain are observed, with one of the cysteine residues of the zinc binding motif being replaced by tyrosine. This suggests that alterations within the zinc finger binding domain of the Rad14 protein cause changes to the damage recognition properties of the protein. The use of the Rad14 protein from the point mutant should assist in experiments investigating the in vitro binding properties of the Rad14 protein to different types of DNA damage. © 1997 by John Wiley & Sons, Ltd.

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Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain

Cited by 368 publications

References 21 publications

DNA Damage Recognition by XPA Protein Promotes Efficient Recruitment of Transcription Factor II H

DNA Damage Recognition by XPA Protein Promotes Efficient Recruitment of Transcription Factor II H

Cell cycle control, checkpoint mechanisms, and genotoxic stress.

Characterization of therad14-2 Mutant ofSaccharomyces cerevisiae: Implications for the Recognition of UV Photoproducts by the Rad14 Protein

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