High Incidence Of Skin Cancer Research Articles

Primary and metastatic cancer of the parotid: comparison of clinical behavior in 232 cases.

Parotid malignancy may develop as a primary cancer of salivary tissue or by metastatic involvement of parotid lymph nodes. The aim of the study was to compare the clinical behavior of primary and metastatic parotid cancers by analyzing patterns of treatment failure and clinical outcomes. Retrospective review of clinical and pathologic data prospectively accessioned onto a computerized database. A prospectively documented series of 232 parotidectomies carried out for treatment of cancer from 1988 to 1999 was reviewed. There were 177 male and 55 female patients with a median age of 65 years (age range, 17-97 y). Median follow-up time was 4 years. Pathological groups included 54 patients with primary parotid cancer, 101 with metastatic cutaneous squamous cell carcinoma, 69 with metastatic melanoma, and 8 with other metastatic cancers. Neck nodes were clinically positive in 12 patients with primary cancer, 24 patients with squamous cell carcinoma, 16 with melanoma, and 2 with other metastatic malignancies. Conservative parotidectomy, preserving the main trunk of the facial nerve, was performed in 185 patients, and 47 patients had a radical parotidectomy sacrificing the facial nerve. There were 54 therapeutic and 110 elective neck dissections. Adjuvant radiotherapy was given to 39 patients with primary cancer, 86 with squamous cell carcinoma, 50 with melanoma, and 8 in the other metastatic group (78% of the patients in the series). Local control rates at 5 years in the four groups were 86%, 75%, 94%, and 100%, respectively (P <.01). Survival rates at 5 years were 77%, 65%, 46%, and 56%, respectively (P <.01). The pattern of parotid malignancy is unique in Australia because of the high incidence of skin cancer, which can metastasize to the parotid gland. Metastatic cutaneous malignancy predominates. The pattern of failure and outcome varied depending on histological findings. Local failure occurred most often in metastatic squamous cell carcinoma, whereas patients with melanoma had the highest incidence of distant spread.

Basal cell carcinoma, squamous cell carcinoma and melanoma of the skin: analysis of the Singapore Cancer Registry data 1968-97.

There has been an alarming recent increase in skin cancer incidence among fair-skinned populations. Information from Asian populations is less readily available. This study examines time trends and ethnic differences of skin cancers among Asians in Singapore. Data from 1968 to 1997 was obtained from the Singapore Cancer Registry, a population-based registry. Age-standardized incidence rates (ASRs) and age-adjusted average annual percentage change, using the Poisson regression model, were calculated. A total of 2650 basal cell carcinomas (BCCs), 1407 squamous cell carcinomas (SCCs) and 281 melanomas were reported. There was an overall increase of skin cancer from 6.0 per 100000 person years (1968-72) to 8.9 per 100000 person years (1993-97). BCC incidence increased 3% annually, melanoma remained constant, and SCC decreased 0.9% annually. BCC ASRs were highest among Chinese, then Malays and Indians. A similar pattern was noted for SCC and melanomas. The incidence rates of skin cancer increased in Singapore during the period 1968-97. Fairer-skinned Chinese had a higher incidence of skin cancer.

Low amounts of the DNA repair XPA protein are sufficient to recover UV-resistance.

DNA integrity is threatened by the damaging effects of physical and chemical agents that can affect its function. Nucleotide excision repair (NER) is one of the most known and flexible mechanisms of DNA repair. This mechanism can recognize and remove damages causing DNA double-helix distortion, including the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine-pyrimidone (6-4) photoproducts, promoted by ultraviolet light (UV). The human syndrome xeroderma pigmentosum (XP) is clinically characterized chiefly by the early onset of severe photosensitivity of the exposed regions of the skin, a very high incidence of skin cancers and frequent neurological abnormalities. The xpa gene seems to be involved during UV damage recognition, in both global genome repair (GGR) and transcription-coupled repair (TCR). The modulation of xpa expression may modify the DNA repair rate in the cell genome, providing a valuable contribution to an understanding of the NER process. The controlled expression of the cDNA xpa in XP12RO deficient cells was achieved through the transfection of a muristerone-A inducible vector, pINXA. The INXA15 clone shows good induction of the XPA protein and total complementation of XP12RO cell deficiency. Overexpression of this protein resulted in UV cell survival comparable to normal control human cells. Moreover, low expression of the XPA protein in these cells is sufficient for total complementation in cellular UV sensitivity and DNA repair activity. These data demonstrate that XPA protein concentration is not a limiting factor for DNA repair.

UV-induced skin carcinogenesis in xeroderma pigmentosum group A (XPA) gene-knockout mice with nucleotide excision repair-deficiency

Nucleotide excision repair (NER) removes a wide variety of lesions from the genome and is deficient in the genetic disorder, xeroderma pigmentosum (XP). In this paper, an in vitro analysis of the XP group A gene product (XPA protein) is reported. Results of an analysis on the pathogenesis of ultraviolet (UV)-B-induced skin cancer in the XPA gene-knockout mouse are also described: (1) contrary to wild type mice, significant bias of p53 mutations to the transcribed strand and no evident p53 mutational hot spots were detected in the skin tumors of XPA-knockout mice. (2) Skin cancer cell lines from UVB-irradiated XPA-knockout mice had a decreased mismatch repair activity and an abnormal cell cycle checkpoint, suggesting that the downregulation of mismatch repair helps cells escape killing by UVB and that mismatch repair-deficient clones are selected for during the tumorigenic transformation of XPA (−/−) cells. (3) The XPA-knockout mice showed a higher frequency of UVB-induced mutation in the rpsL transgene at a low dose of UVB-irradiation than the wild type mice. CC→TT tandem transition, a hallmark of UV-induced mutation, was detected at higher frequency in the rpsL transgene in the XPA-knockout mice than the wild type mice. This rpsL/XPA mouse system will be useful for further analysing the role of NER in the mutagenesis induced by various carcinogens. (4) The UVB-induced immunosuppression was greatly enhanced in the XPA-knockout mice. It is possible that an enhanced impairment of the immune system by UVB irradiation is involved in the high incidence of skin cancer in XP.

Misconceptions in Australian students' understanding of Ozone depletion

Declining levels of stratospheric ozone resulting from anthropogenic source gases is internationally recognized as one of the Earth’s most important environmental issues. In the last twenty years, global ozone trends show that concentrations are decreasing by 2-5% per decade in the middle latitudes. The societal concern is that with decreasing concentrations of ozone, the amount of the Sun’s ultra-violet (UV) radiation reaching the Earth’s surface will increase and potentially damage both human and other biological life. The goal of this pilot study is to investigate whether misconceptions exist in Australian students’ understanding of ozone depletion and the relationship to skin cancer in Australia. Students from year 3 through first year university were questioned about issues related to ozone depletion and skin cancer. A simple experiment is developed to examine whether some student concepts can be altered through the use of visual diagrams. Included in this paper is an update on the current status of ozone depletion over Australia, and the relati onship to UV radiation and skin cancer. In addition, a brief review of newspaper articles written about ozone depletion is conducted to explore what possible role the media plays in public misconceptions. Understanding the origin of students’ ideas can assist teachers in producing more effective study programs 1 and may be useful in developing a national strategy for teaching environmental issues. In Australia there is a particular interest in sun related issues because of the population’s high incidence of skin cancer. For example, in 1995 approximately 270,000 cases of nonmelanocytic skin cancer were diagnosed. This suggests that nearly two in three Australian residents will be treated for some non-melanocytic skin cancer during their lifetime. For the more life-threatening melanoma skin cancer, over 7,000 cases were diagnosed in Australia, with almost 1,000 fatalities reported. It is estimated that the cost of treating skin cancer in Australia is between $300-500 million per year. 2 In an attempt to improve the awareness of the dangers of sun related diseases, the government initiated a number of sun awareness campaigns to educate the public. These campaigns have been highly effective in getting across the message of the sun’s potential harm. In a survey by the Victorian Anti Cancer Council, almost 80% of respondents had heard the term ‘Sun Smart,’ and correctly understood what the phrase meant. 3 Student awareness of the sun and issues related to ozone depletion are also particularly strong. In a recent survey of high school students from Melbourne and Brisbane, the destruction of the ozone layer was identified as the most important environmental issue facing Australia and the

Using health communications for primary prevention of skin cancer: CDC's Choose Your Cover campaign.

SKIN CANCER IS THE MOST COMMON KIND of cancer in the United States, with approximately 1.3 million cases of highly curable basal cell or squamous cancers expected to occur this year. It is anticipated that 47,700 people will be diagnosed with melanoma, the most serious form of cancer, and over half of those diagnosed will be women.1 Current etiological evidence suggests a causal link between excessive and unprotected sun exposure and skin cancer, expecially sun exposure received early in life.2,3 According to experts, primary prevention of skin cancer involves one or more of the recommended sun protection behaviors: staying out of the sun between 10 AM and 4 PM , using protective clothing (hats, long sleeves, and long pants), seeking shade, and using sunscreen. Following these recommendations may prevent skin cancer or reduce the high incidence of skin cancer observed in the United States.4 Studies conducted in the United States indicate that most Americans, adults and children, do not follow recommended sun protection practices. When they do, however, sunscreen is clearly the method of choice. The reported use of sunscreen and other protection measures varies considerably depending on age, gender, setting, and how the behavior is measured. Protective clothing and sunglasses are rarely used or observed in children, hat use is more common, and reported sunscreen use ranges from 32% to 53%. Overall, women are far more likely than men to engage in prevention.5 The Centers for Disease Control and Prevention (CDC) took up the challenge of promoting sun protection practices in 1998, when they launched their 5-year skin cancer prevention campaign, called “Choose Your Cover” (CYC). The goals of the campaign include influencing social norms related to sun protection and tanned skin and increasing awareness, knowledge, and behaviors related to skin cancer.

Evidence for the involvement of nucleotide excision repair in the removal of abasic sites in yeast.

In eukaryotes, DNA damage induced by ultraviolet light and other agents which distort the helix is removed by nucleotide excision repair (NER) in a fragment approximately 25 to 30 nucleotides long. In humans, a deficiency in NER causes xeroderma pigmentosum (XP), characterized by extreme sensitivity to sunlight and a high incidence of skin cancers. Abasic (AP) sites are formed in DNA as a result of spontaneous base loss and from the action of DNA glycosylases involved in base excision repair. In Saccharomyces cerevisiae, AP sites are removed via the action of two class II AP endonucleases, Apn1 and Apn2. Here, we provide evidence for the involvement of NER in the removal of AP sites and show that NER competes with Apn1 and Apn2 in this repair process. Inactivation of NER in the apn1Delta or apn1Delta apn2Delta strain enhances sensitivity to the monofunctional alkylating agent methyl methanesulfonate and leads to further impairment in the cellular ability to remove AP sites. A deficiency in the repair of AP sites may contribute to the internal cancers and progressive neurodegeneration that occur in XP patients.

Skin cancer in liver transplant recipients.

Skin cancer is the most common malignancy arising in the posttransplantation setting. Multiple factors contribute to the high risk for cutaneous carcinoma in immunosuppressed organ-transplant recipients. We review the phenomenon of skin cancer in solid-organ transplant recipients and further delineate the problem in the context of liver transplantation. Skin cancer is a significant medical and surgical problem for organ-transplant recipients. With prolonged allograft function and patient survival, the majority of solid-organ transplant recipients will eventually develop skin cancer. Although squamous cell carcinoma is the most common cutaneous malignancy in this population, basal cell carcinoma, melanoma, and Kaposi's sarcoma, as well as uncommon skin malignancies, may occur. Highly susceptible patients may develop hundreds of squamous cell carcinomas, which may be life threatening. Management strategies focus on regular full-skin and nodal examination, aggressive treatment of established malignancies, and prophylactic measures to reduce the risk for additional photodamage and malignant transformation. Skin cancer is a substantial cause of morbidity and even mortality among solid-organ transplant recipients. As a byproduct of immunosuppression, liver transplant recipients experience a high incidence of skin cancer and should be educated and managed accordingly.

Fidelity of Human DNA Polymerase η

Xeroderma pigmentosum (XP) patients are highly sensitive to sunlight, and they suffer from a high incidence of skin cancers. The variant form of XP results from mutations in the hRAD30A gene, which encodes the DNA polymerase in humans, hPol(eta). Of the eukaryotic DNA polymerases, only human Pol(eta) and its yeast counterpart have the ability to replicate DNA containing a cis-syn thymine-thymine (T-T) dimer. Here we measure the fidelity of hPol(eta) on all four nondamaged template bases and at each thymine residue of a cis-syn T-T dimer. Opposite all four nondamaged template bases, hPol(eta) misincorporates nucleotides with a frequency of approximately 10(-2)-10(-3), and importantly, hPol(eta) synthesizes DNA opposite the T-T dimer with the same accuracy and efficiency as opposite the nondamaged DNA. The low fidelity of hPol(eta) may derive from a flexible active site that renders the enzyme more tolerant of geometric distortions in DNA and enables it to synthesize DNA past a T-T dimer.

HRAD30 mutations in the variant form of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by a high incidence of skin cancers. Yeast RAD30 encodes a DNA polymerase involved in the error-free bypass of ultraviolet (UV) damage. Here it is shown that XP variant (XP-V) cell lines harbor nonsense or frameshift mutations in hRAD30, the human counterpart of yeast RAD30. Of the eight mutations identified, seven would result in a severely truncated hRad30 protein. These results indicate that defects in hRAD30 cause XP-V, and they suggest that error-free replication of UV lesions by hRad30 plays an important role in minimizing the incidence of sunlight-induced skin cancers.

Ultraviolet Radiation-Induced Suppression of Natural Killer Cell Activity is Enhanced in Xeroderma Pigmentosum Group A (XPA) Model Mice

Xeroderma pigmentosum group A gene-deficient mice easily develop skin cancers by ultraviolet radiation. Natural killer cells play an important part in tumor surveillance. To study whether ultraviolet radiation-induced suppression of natural killer cell function is involved in the high incidence of skin tumors in patients with xeroderma pigmentosum, we analyzed the number and activity of natural killer cells in ultraviolet B-irradiated xeroderma pigmentosum A model mice. The number of natural killer cells in peripheral blood significantly decreased after ultraviolet B-irradiation only in xeroderma pigmentosum A mice, but those in the spleen were not affected. As compared with the wild-type mice, the xeroderma pigmentosum A mice displayed a higher level of spontaneous splenic natural killer cell activity (10%-15% vs 3%) and inducible natural killer activity (30%-50% vs 20%-25%) after injection of polyinosinic:polycytidylic acid. At 24 h after the last irradiation of three and five daily consecutive exposures to 500 mJ per cm2-ultraviolet B, however, the natural killer activity in xeroderma pigmentosum A mice decreased to 60 and 30% of the preirradiated level, respectively, but it did not in the wild-type mice. The depression of natural killer activity in xeroderma pigmentosum A mice recovered to a normal level at 10 and 15 d after the last irradiation, respectively. The high incidence of skin cancers in xeroderma pigmentosum patients may be mainly due to a defect in the repair of ultraviolet-damaged DNA of cutaneous cells, and possibly also due to an intensified ultraviolet-induced immunosuppression. Moreover, the present study suggests that the enhanced ultraviolet-induced impairment of natural killer function could be partially involved in cancer development.

Incidence of skin cancers and precancerous lesions in Japanese--risk factors and prevention.

An examination of the occurrence of skin cancers and precancerous lesions among residents of Kasai City (34 degrees 56' N) since 1992, and of le-island (25 degrees 10' N) since 1993, has been conducted to characterize the prevalence and incidence of skin cancers in Japanese people and to evaluate risk and preventive factors. The mean prevalence of actinic keratosis (AK) in residents of Kasai City and le-island was 203.33 and 756.26, respectively, indicating that twice the dose of UVB radiation causes a 3-4 fold higher incidence of AK, although life styles, including types of occupations, differ in these two locations. Working outdoors, having skin type I and/or a history of severe sunburns during childhood were found to be important risk factors, while the use of cosmetics after 20 years of age was a protective factor, for AK and possibly for skin cancers. Further, sunscreen use among males over 60 years of age in Kasai City from 1994 through 1998 suggested that sunscreen use may reduce AK development in older people. Four and 12 cases of skin cancers were found in residents of Kasai City (from 1992 to 1997) and on le-island (from 1993 to 1998), respectively. These numbers are too small to establish the prevalence of skin cancer in Japanese, but indicate that people living in areas of higher ambient solar radiation have a higher incidence of skin cancer. This epidemiological study strongly indicates that sun protection is the major modality to reduce sun-induced cutaneous tumors in Japanese.

UV-induced mutations and skin cancer: how important is the link?

Studies with patients having the inherited DNA repair disorders xeroderma pigmentosum (XP), Cockayne syndrome (CS), and sun-sensitive trichthiodystrophy (TTD) have shown that neither the defect in repair nor the consequent elevated frequency of sunlight-induced mutations in the skin is sufficient to account for the classically high incidence of skin cancer in XP patients. The possible ways in which different mutations in the XP(D) gene and deficiencies in the immune system may be involved are discussed.

208 Mouse langerhans cells do not express high affinity IgE receptor

Nucleotide excision repair (NER) removes a wide variety of lesions from the genome and is deficient in the genetic disorder, xeroderma pigmentosum (XP). In this paper, an in vitro analysis of the XP group A gene product (XPA protein) is reported. Results of an analysis on the pathogenesis of ultraviolet (UV)-B-induced skin cancer in the XPA gene-knockout mouse are also described: (1) contrary to wild type mice, significant bias of p53 mutations to the transcribed strand and no evident p53 mutational hot spots were detected in the skin tumors of XPA-knockout mice. (2) Skin cancer cell lines from UVB-irradiated XPA-knockout mice had a decreased mismatch repair activity and an abnormal cell cycle checkpoint, suggesting that the downregulation of mismatch repair helps cells escape killing by UVB and that mismatch repair-deficient clones are selected for during the tumorigenic transformation of XPA (−/−) cells. (3) The XPA-knockout mice showed a higher frequency of UVB-induced mutation in the rpsL transgene at a low dose of UVB-irradiation than the wild type mice. CC→TT tandem transition, a hallmark of UV-induced mutation, was detected at higher frequency in the rpsL transgene in the XPA-knockout mice than the wild type mice. This rpsL/XPA mouse system will be useful for further analysing the role of NER in the mutagenesis induced by various carcinogens. (4) The UVB-induced immunosuppression was greatly enhanced in the XPA-knockout mice. It is possible that an enhanced impairment of the immune system by UVB irradiation is involved in the high incidence of skin cancer in XP.

An assessment of the suitability of Mohs micrographic surgery in patients aged 90 years and older.

One option for the treatment of cutaneous tumors in the very elderly has been simple observation. However, the combination of an increasing elderly population and a concomitant high incidence of skin cancer will make this problem more common. To assess the suitability of Mohs micrographic surgery as a treatment modality for skin cancer in the 90 years and older age group. A group of patients who underwent Mohs surgery from January 1988 to August 1996 aged 90 years and older was identified, and tumor type, site, comorbid medical conditions, medications, and surgical complications were recorded. A total of 106 basal cell carcinomas (BCCs), 33 squamous cell carcinomas (SSC), six melanomas, and one basosquamous carcinoma were resected from 115 patients with an average age of 92.4 years. The overall ratio of BCC/SCC was 3.2 BCCs occurred most commonly on the face; SCCs were found more frequently on the cheeks. Patients had an average of 1.9 comorbid medical conditions and took an average of 2.3 regular medications. One complication occurred. Mohs surgery is a safe and effective therapy for those over 90 years of age.

Skin type distribution and skin disease in Ireland

The Irish are generally considered to have a fair complexion. We surveyed the distribution of skin type in an Irish city population (n = 1000). Skin type prevalence was as follows: type 1: 26%, type 2: 49.6%, type 3: 19.7%, type 4: 4.3%, type 5: 0.3%, type 6: 0.1%. Sunbeds were used by 16% of the population. Malignant melanoma occurred in 1.4% of patients, non-melanoma skin cancer in 6%. The high frequency of sunbed use in a fair skinned population and the high incidence of skin cancer is disturbing and highlights the need for ongoing public health education regarding ultraviolet radiation risks.

Skin cancer prevention education: a national survey of YMCAs.

High skin cancer incidence and mortality rates have created a need for skin cancer prevention education. Children are an important target for this education, as overexposure to sun and sunburns at an early age have been linked to the development of skin cancer. This study identified the prevalence of skin cancer prevention education and the need for this education at YMCA swim classes. This study also assessed the feasibility of implementing Project SUNWISE, an existing skin cancer prevention curriculum, developed for YMCA swim classes. A 51-item survey was mailed to Aquatics Directors at all YMCAs with outdoor pools. Based on a 63% response rate (N = 208), only 28% of YMCAs thought the children in their swim classes were adequately protected from the sun, and only 28% offered skin protection or sun safety education in swim classes. Only 50% of YMCAs trained their swim instructors on skin cancer prevention. While 91% of YMCAs had one or more sun protection items near the pool (e.g., sunscreen, umbrella, covered area), 93% of YMCAs saw the need for additional protection. The majority of YMCAs (95%) were willing to incorporate a skin cancer prevention education curriculum, similar to Project SUNWISE, into their swim classes. This study emphasized the need for more skin cancer prevention education programs targeting children and examined the correlates of skin cancer prevention education at YMCAs. Geographic region, percent of possible sunshine, and ultraviolet radiation were significantly associated with the skin cancer prevention education program status at the YMCAs.

Photochemical sensitization by azathioprine and its metabolites. Part 3. A direct EPR and spin-trapping study of light-induced free radicals from 6-mercaptopurine and its oxidation products.

Sunlight has been implicated in the high incidence of skin cancer found in patients receiving 6-mercaptopurine (PSH) in the form of its pro-drug azathioprine. In this study we have used EPR spectroscopy in conjunction with the spin-trapping technique to determine whether PSH and its metabolic or photochemical oxidation products generate highly reactive free radicals upon UV irradiation. When an aqueous anaerobic solution (pH 5 or 9) of PSH (pKa = 7.7) and either 2-methyl-2-nitrosopropane (MNP) or nitromethane (NM) were irradiated (lambda > 300 nm) with a Xe arc lamp, the corresponding purine-6-thiyl (PS.) radical adduct and the reduced form of the spin trap (MNP/H. or CH3NO2.-) were observed. However, no radical adducts were detected when PSH and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were irradiated (lambda = 320 nm) in oxygen-free buffer. These findings suggest that PSH does not photoionize but that instead MNP and NM are reduced by direct electron transfer from excited state PSH, 1.3(PSH)*. In aerobic solution, oxygen can act as an electron acceptor and the O2.- and PS. radicals are formed and trapped by DMPO. 6-Mercaptopurine did photoionize when irradiated with a Nd:YAG laser at 355 nm as evidenced by the appearance of the DMPO/H.(eq- + H+) adduct, which decreased in intensity in the presence of N2O. 1.3(6-Mercaptopurine)* oxidized ascorbate, formate and reduced glutathione to the corresponding ascorbyl, CO2.- or glutathiyl radicals. The photochemical behavior of 6-thioxanthine and 6-thiouric acid was similar to PSH. However, the excited states of these metabolic oxidation products exhibited stronger reducing properties than 1.3(PSH)*.(ABSTRACT TRUNCATED AT 250 WORDS)

Human xeroderma pigmentosum group G gene encodes a DNA endonuclease.

Because of defective nucleotide excision repair of ultraviolet damaged DNA, xeroderma pigmentosum (XP) patients suffer from a high incidence of skin cancers. Cell fusion studies have identified seven XP complementation groups, A to G. Previous studies have implicated the products of these seven XP genes in the recognition of ultraviolet-induced DNA damage and in incision of the damage-containing DNA strand. Here, we express the XPG-encoded protein in Sf9 insect cells and purify it to homogeneity. We demonstrate that XPG is a single-strand specific DNA endonuclease, thus identifying the catalytic role of the protein in nucleotide excision repair. We suggest that XPG nuclease acts on the single-stranded region created as a result of the combined action of the XPB helicase and XPD helicase at the DNA damage site.

Human xeroderma pigmentosum group D gene encodes a DNA helicase.

Xeroderma pigmentosum (XP), a genetically heterogeneous human disease, results from a defect in nucleotide excision repair of ultraviolet-damaged DNA. XP patients are extremely sensitive to sunlight and suffer from a high incidence of skin cancers. Cell fusion studies have identified seven XP complementation groups, A-G. Group D is of particular interest as mutations in this gene can also cause Cockayne's syndrome and trichothiodystrophy. The XPD gene was initially named ERCC2 (excision repair cross complementing) as it was cloned using human DNA to complement the ultraviolet sensitivity of a rodent cell line. We have purified the XPD protein to near homogeneity and show that it possesses single-stranded DNA-dependent ATPase and DNA helicase activities. We tested whether XPD can substitute for its yeast counterpart RAD3, which is essential for excision repair and for cell viability. Expression of the XPD gene in Saccharomyces cerevisiae can complement the lethality defect of a mutation in the RAD3 gene, suggesting that XPD is an essential gene in humans.