Human ERCC5 cDNA-Cosmid Complementation for Excision Repair and Bipartite Amino Acid Domains Conserved with RAD Proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe

MacInnes, Mark A.; Dickson, Juleen; Hernandez, R R; Learmonth, D; Lin, Grace; Mudgett, John S.; Park, M S; Schauer, Susan; Reynolds, Richard J.; Strniste, G.F.

doi:10.1128/mcb.13.10.6393-6402.1993

Cited by 4 publications

(1 citation statement)

References 63 publications

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“…34,35 In the cases of the XPC and CSA genes, direct cloning from human cells was achieved using episomally replicating plasmids containing viral replication systems and human cDNA libraries. 36,37 Other genes, such as XPG, 38,39 XPF, 40,41 hHR23B 42 (human homologue of Saccharomyces cereVisiae RAD23) and more recently TTDA 43 (encoding for the 10th subunit of the TFIIH complex) were identified by chance or by sequence homology with repair genes discovered in other organisms. Interestingly, the cloning of XPG was entirely serendipitouss it was discovered as a second open reading frame of a clone isolated in the search for a gene involved in tRNA transcription.…”

Section: From the Complementation Groups To The Genesmentioning

confidence: 99%

Molecular Mechanisms of Mammalian Global Genome Nucleotide Excision Repair

2005

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Section: From the Complementation Groups To The Genesmentioning

confidence: 99%

Molecular Mechanisms of Mammalian Global Genome Nucleotide Excision Repair

2005

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RETRACTED: A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: Implications for a second XPG function

Nouspikel

Lalle

Leadon

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

148

120

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Xeroderma pigmentosum (XP) patients have defects in nucleotide excision repair (NER), the versatile repair pathway that removes UV-induced damage and other bulky DNA adducts. Patients with Cockayne syndrome (CS), another rare sun-sensitive disorder, are specifically defective in the preferential removal of damage from the transcribed strand of active genes, a process known as transcription-coupled repair. These two disorders are usually clinically and genetically distinct, but complementation analyses have assigned a few CS patients to the rare XP groups B, D, or G. The XPG gene encodes a structure-specific endonuclease that nicks damaged DNA 3′ to the lesion during NER. Here we show that three XPG/CS patients had mutations that would produce severely truncated XPG proteins. In contrast, two sibling XPG patients without CS are able to make full-length XPG, but with a missense mutation that inactivates its function in NER. These results suggest that XPG/CS mutations abolish interactions required for a second important XPG function and that it is the loss of this second function that leads to the CS clinical phenotype.

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Comparison of the 5′ nuclease activities of Taq DNA polymerase and its isolated nuclease domain

Lyamichev

Brow

Varvel

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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Many eubacterial DNA polymerases are bifunctional molecules having both polymerization (P) and 5 nuclease (N) activities, which are contained in separable domains. We previously showed that the DNA polymerase I of Thermus aquaticus (TaqNP) endonucleolytically cleaves DNA substrates, releasing unpaired 5 arms of bifurcated duplexes. Here, we compare the substrate specificities of TaqNP and the isolated 5 nuclease domain of this enzyme, TaqN. Both enzymes are significantly activated by primer oligonucleotides that are hybridized to the 3 arm of the bifurcation; optimal stimulation requires overlap of the 3 terminal nucleotide of the primer with the terminal base pair of the duplex, but the terminal nucleotide need not hybridize to the complementary strand in the substrate. In the presence of Mn 2؉ ions, TaqN can cleave both RNA and circular DNA at structural bifurcations. Certain anti-TaqNP mAbs block cleavage by one or both enzymes, whereas others can stimulate cleavage of nonoptimal substrates.Structure-sensing nucleases are ubiquitous in biology, being essential for both the synthesis and the repair of DNA (1-12). Several of these enzymes cleave bifurcated duplex DNAs endonucleolytically, releasing the single-stranded 5Ј arm (13). The 5Ј nuclease activity accounts for the ability of these enzymes to remove RNA primers or damaged DNA nucleotides (for review, see ref. 15). In eubacteria, 5Ј nucleases are discrete domains in the DNA polymerases, but in Eukarya and Archaea, they are separate from DNA polymerases and have been called DNA endonuclease IV (1) or, more recently, FEN1 nuclease (16). We refer to the DNA polymerase of T. aquaticus as TaqNP, because it contains both the nuclease and polymerase domains in a single polypeptide; likewise, we refer to the isolated nuclease domain of this enzyme as TaqN.We previously showed that the 5Ј nuclease activity of TaqNP is increased by several orders of magnitude if an oligonucleotide (the primer) is hybridized to the 3Ј arm of the bifurcation (13). The role of the primer in the activation and location of cleavage was unclear. We also showed that cleavage required a free 5Ј end of the single-stranded arm, indicating that the enzyme moved to the site of cleavage by threading the single strand through a hole or a narrow groove in the enzyme, and a requirement for a free 5Ј end was subsequently observed for the calf FEN1 nuclease (14). Recent crystal structures have demonstrated the existence of helical arches or holes in a similar nuclease, T5 exonuclease, as well as in .The influence of the polymerase domain on the activity of the 5Ј nuclease has not been determined. Structure-function probing of the nuclease and polymerase domains of TaqNP by using mAbs generated against the intact enzyme (22) demonstrated some functional overlap between the nuclease and polymerase domains of the enzyme (23). Here, we compare the activities and substrate requirements of TaqN, the isolated 5Ј nuclease of TaqNP, and the same functional domain when it is part of the intact TaqNP h...

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Human ERCC5 cDNA-Cosmid Complementation for Excision Repair and Bipartite Amino Acid Domains Conserved with RAD Proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe

Cited by 4 publications

References 63 publications

Molecular Mechanisms of Mammalian Global Genome Nucleotide Excision Repair

Molecular Mechanisms of Mammalian Global Genome Nucleotide Excision Repair

RETRACTED: A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: Implications for a second XPG function

Comparison of the 5′ nuclease activities of Taq DNA polymerase and its isolated nuclease domain

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