Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH

Coin, Frédéric; Bergmann, Etienne; Tremeau‐Bravard, Alexandre; Egly, Jean‐Marc

doi:10.1093/emboj/18.5.1357

Cited by 176 publications

(162 citation statements)

References 36 publications

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“…These mutations are associated with loss of other functions such as transcriptional activity (41). A recent study suggests that perhaps a similar development has occurred with BACH1.…”

Section: Discussionmentioning

confidence: 93%

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations

Cantor

Drapkin²,

Zhang³

et al. 2004

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

219

247

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BACH1 is a nuclear protein that directly interacts with the highly conserved, C-terminal BRCT repeats of the tumor suppressor, BRCA1. Mutations within the BRCT repeats disrupt the interaction between BRCA1 and BACH1, lead to defects in DNA repair, and result in breast and ovarian cancer. BACH1 is necessary for efficient double-strand break repair in a manner that depends on its association with BRCA1. Moreover, some women with early-onset breast cancer and no abnormalities in either BRCA1 or BRCA2 carry germline BACH1 coding sequence changes, suggesting that abnormal BACH1 function contributes to tumor induction. Here, we show that BACH1 is both a DNA-dependent ATPase and a 5′-to-3′ DNA helicase. In two patients with early-onset breast cancer who carry distinct germline BACH1 coding sequence changes, the resulting proteins are defective in helicase activity, indicating that these sequence changes disrupt protein function. These results reinforce the notion that mutant BACH1 participates in breast cancer development

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“…These mutations are associated with loss of other functions such as transcriptional activity (41). A recent study suggests that perhaps a similar development has occurred with BACH1.…”

Section: Discussionmentioning

confidence: 93%

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations

Cantor

Drapkin²,

Zhang³

et al. 2004

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

219

247

View full text Add to dashboard Cite

show abstract

“…We next addressed the role of ATP, which is required for the activity of the XPB and XPD helicases of TFIIH (33)(34)(35) in modulating the footprinting pattern of the damaged DNA around the lesion (36). We first observed that ATP does not modify the XPC/HR23B footprinting pattern of the damaged DNA (Fig.…”

Section: Resultsmentioning

confidence: 99%

Ordered Conformational Changes in Damaged DNA Induced by Nucleotide Excision Repair Factors

Tapias

Auriol

Forget

et al. 2004

Journal of Biological Chemistry

141

152

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In response to genotoxic attacks, cells activate sophisticated DNA repair pathways such as nucleotide excision repair (NER), which consists of damage removal via dual incision and DNA resynthesis. Using permanganate footprinting as well as highly purified factors, we show that NER is a dynamic process that takes place in a number of successive steps during which the DNA is remodeled around the lesion in response to the various NER factors. XPC/HR23B first recognizes the damaged structure and initiates the opening of the helix from position ؊3 to ؉6. TFIIH is then recruited and, in the presence of ATP, extends the opening from position ؊6 to ؉6; it also displaces XPC downstream from the lesion, thereby providing the topological structure for recruiting XPA and RPA, which will enlarge the opening. Once targeted by XPG, the damaged DNA is further melted from position ؊19 to ؉8. XPG and XPF/ERCC1 endonucleases then cut the damaged DNA at the limit of the opened structure that was previously "labeled" by the positioning of XPC/HR23B and TFIIH.To counteract the detrimental effect of genotoxic attacks, cells activate sophisticated and specific DNA repair pathways. Damage induced by UV radiation, environmental agents, and anticancer drugs are removed by two distinct nucleotide excision repair (NER) 1 subpathways, namely global genome repair (GGR), which eliminates lesions from the entire genome, and transcription-coupled repair (TCR), a specialized pathway that repairs damages on a transcribed strand of active genes (1-3). Human NER involves the ordered action of factors in dual incision and DNA repair resynthesis steps (4). Any mutation that affects either the enzymatic activity or the ordered assembly of the dual incision complex leads to genetic disorders such as xeroderma pigmentosum, trichothiodystrophy, or Cockayne syndrome (5, 6).In global genome repair, the dual incision is a multistep process that results from the coordinated action of XPC/ HR23B, TFIIH, XPA, RPA, XPG, and XPF/ERCC1, resulting in the removal of the damaged oligonucleotide (4, 7, 8). After being recognized by the XPC/HR23B complex, the damaged DNA structure is targeted by TFIIH, which recruits the other factors upon the addition of ATP (9 -11). The unwound DNA is then incised by the two endonucleases XPG and XPF/ERCC1 on the 3Ј and 5Ј side of the lesion, respectively (12-15), leaving a gap structure that is filled up by the DNA polymerase ⑀ or ␦ and the accompanying factors PCNA, RF-C, RPA, and DNA ligase I (16). Whether or not the NER reaction occurs by sequential arrival of the various factors or by a pre-assembled complex referred to as the repairosome or the holoenzyme is still under debate (17)(18)(19). Although the hypothesis of the sequential assembly, which has gained a lot of support from recent biological studies, seems to be more accepted, the order of assembly of the NER factors on the damaged DNA and their contribution to the DNA remodeling to allow the repair are not fully understood (10,20,21). As an example, to further learn abou...

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“…The XPD gene encodes a helicase that is a component of the transcription factor TFIH. Mutations in the XPD gene can diminish the activity of TFIH complexes increasing the likelihood of repair defects, transcription defects and abnormal response to apoptosis (Sung et al, 1993;Coin et al, 1999). The low activity of repair defects may induce the progression of carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

DNA Repair Gene ERCC1 and XPD Polymorphisms Predict Glioma Susceptibility and Prognosis

Chen

Yao²,

Zhao³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Aims: We conducted a case-control study in a Chinese population to clarify the association between polymorphisms in ERCC1 and XPD and susceptibility and survival of glioma. Methods: A total of 393 cases and 410 controls were selected from March 2007 to December 2011. Genotyping of ERCC1 and XPD was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. All analyses were performed using the STATA statistical package. Results: Polymorphisms in ERCC1 118C/T, ERCC1 8092C/A and XPD Asp312Asn showed no statistically significant difference between glioma cases and controls. However, individuals with the XPD 751Gln/Gln genotype had an increased risk of developing glioma compared with those with the Lys/Lys genotype (adjusted OR=1.64, 95% CI: 1.06-2.89). The ERCC1 118T/T genotype was associated with significantly higher median survival than the ERCC1 C/C genotype (HR=0.67, 95%CI=0.35-0.96). In addition, individuals with XPD 751Gln/Gln had a lower median survival time than XPD Lys/Lys carriers (HR=0.54, 95%CI=0.37-0.93). Conclusion: In conclusion, we observed that the XPD 751Gln/Gln genotype is associated with glioma susceptibility, and ERCC1 118 T/T and XPD 751Gln/Gln genotypes confer a significantly better prognosis.

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Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH

Cited by 176 publications

References 36 publications

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations

Ordered Conformational Changes in Damaged DNA Induced by Nucleotide Excision Repair Factors

DNA Repair Gene ERCC1 and XPD Polymorphisms Predict Glioma Susceptibility and Prognosis

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