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Biomedical subjects

J L Campbell

Publications and source records attributed to J L Campbell.

At least 19 recordsLinked to original sources
PubMed2006

Home-based versus hospital-based rehabilitation after myocardial infarction: A randomized trial with preference arms--Cornwall Heart Attack Rehabilitation Management Study (CHARMS).

BACKGROUND: Participation in cardiac rehabilitation after acute myocardial infarction is sub-optimal. Offering home-based rehabilitation may improve uptake. We report the first randomized study of cardiac rehabilitation to include patient preference. AIM: To compare the clinical effectiveness of a home-based rehabilitation with hospital-based rehabilitation after myocardial infarction and to determine whether patient choice affects clinical outcomes. DESIGN: Pragmatic randomized controlled trial with patient preference arms. SETTING: Rural South West England. METHODS: Patients admitted with uncomplicated myocardial infarction were offered hospital-based rehabilitation classes over 8-10 weeks or a self-help package of six weeks' duration (the Heart Manual) supported by a nurse. Primary outcomes at 9 months were mean depression and anxiety scores on the Hospital Anxiety Depression scale, quality of life after myocardial infarction (MacNew) score and serum total cholesterol. RESULTS: Of the 230 patients who agreed to participate, 104 (45%) consented to randomization and 126 (55%) chose their rehabilitation programme. Nine month follow-up data were available for 84/104 (81%) randomized and 100/126 (79%) preference patients. At follow-up no difference was seen in the change in mean depression scores between the randomized home and hospital-based groups (mean difference: 0; 95% confidence interval, -1.12 to 1.12) nor mean anxiety score (-0.07; -1.42 to 1.28), mean global MacNew score (0.14; -0.35 to 0.62) and mean total cholesterol levels (-0.18; -0.62 to 0.27). Neither were there any significant differences in outcomes between the preference groups. CONCLUSIONS: Home-based cardiac rehabilitation with the Heart Manual was as effective as hospital-based rehabilitation for patients after myocardial infarction. Choosing a rehabilitation programme did not significantly affect clinical outcomes.

Chi-Square Distribution↗
PubMed2006

Home-based cardiac rehabilitation versus hospital-based rehabilitation: a cost effectiveness analysis.

BACKGROUND: Home-based cardiac rehabilitation offers an alternative to traditional, hospital-based cardiac rehabilitation. AIM: To compare the cost effectiveness of home-based cardiac rehabilitation and hospital-based cardiac rehabilitation. METHODS: 104 patients with an uncomplicated acute myocardial infarction and without major comorbidity were randomized to receive home-based rehabilitation (n=60) i.e. nurse facilitated, self-help package of 6 weeks' duration (the Heart Manual) or hospital-based rehabilitation for 8-10 weeks (n=44). Complete economic data were available in 80 patients (48 who received home-based rehabilitation and 32 who received hospital-based rehabilitation). Healthcare costs, patient costs, and quality of life (EQ-5D4.13) were assessed over the 9 months of the study. RESULTS: The cost of running the home-based rehabilitation programme was slightly lower than that of the hospital-based programme (mean (95% confidence interval) difference - 30 pounds sterling (- 45 pounds sterling to - 12 pounds sterling) [-44 euro, -67 euro to -18 euro] per patient. The cost difference was largely the result of reduced personnel costs. Over the 9 months of the study, no significant difference was seen between the two groups in overall healthcare costs (78 pounds sterling, - 1102 pounds sterling to 1191 pounds sterling [-115 euro, -1631 euro to -1763 euro] per patient) or quality adjusted life-years (-0.06 (-0.15 to 0.02)). The lack of significant difference between home-based rehabilitation and hospital-based rehabilitation did not alter when different costs and different methods of analysis were used. CONCLUSIONS: The health gain and total healthcare costs of the present hospital-based and home-based cardiac rehabilitation programmes for patients after myocardial infarction appear to be similar. These initial results require affirmation by further economic evaluations of cardiac rehabilitation in different settings.

Cost-Benefit Analysis↗
PubMed2006

Prevalence and clinical implications of the inter-arm blood pressure difference: A systematic review.

A blood pressure (BP) difference between arms was first reported over 100 years ago. Knowledge of its prevalence and relevance to the accurate measurement of BP remains poor. Current hypertension guidelines do not emphasise it. The objectives of this study were to establish the best estimate of prevalence of the inter-arm difference (IAD) in the population, to consider its implications for accurate BP measurement and treatment, and to discuss its aetiology and potential as a risk marker for cardiovascular disease. Systematic literature review was carried out. The data sources were Medline EMBASE and CINAHL databases, and Index of Theses. Studies reporting prevalence rates of IAD were retrieved and considered for inclusion against explicit methodological criteria. Point prevalence rates were extracted and weighted mean prevalence rates calculated. The main outcome measures were weighted mean prevalences of systolic IAD > or =10 and > or =20 mm Hg and of diastolic IAD > or =10 mm Hg. Thirty-one studies were identified. Most had methodological weaknesses; only four met the inclusion criteria. Pooled prevalences of the IAD from these four studies were 19.6% systolic > or =10 mm Hg (95% CI 18.0-21.3%), 4.2% systolic > or =20 mm Hg (95% CI 3.4-5.1%) and 8.1% diastolic > or =10 mm Hg (95%CI 6.9-9.2%). In conclusion, an IAD is present in a substantial number of patients and should be looked for whenever diagnosis and treatment depend on accurate measurements of BP. The importance of an IAD should be better emphasised in current hypertension management guidelines. There is evidence associating an IAD with peripheral vascular disease, raising the possibility that its presence may predict cardiovascular events.

Algorithms↗
PubMed2006

Acupuncture and related interventions for smoking cessation.

BACKGROUND: Acupuncture and related techniques are promoted as a treatment for smoking cessation in the belief that they may reduce nicotine withdrawal symptoms. OBJECTIVES: The objectives of this review are to determine the effectiveness of acupuncture and the related interventions of acupressure, laser therapy and electrostimulation, in smoking cessation in comparison with no intervention, sham treatment, or other interventions. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group specialized register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, BIOSIS Previews, PsycINFO, Science and Social Sciences Citation Index, AMED and CISCOM. Date of last search January 2005. SELECTION CRITERIA: Randomized trials comparing a form of acupuncture, acupressure, laser therapy or electrostimulation with either no intervention, sham treatment or another intervention for smoking cessation. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of smokers recruited, the nature of the acupuncture and control procedures, the outcome measures, method of randomization, and completeness of follow up. We assessed abstinence from smoking at the earliest time-point (before six weeks), and at the last measurement point between six months and one year. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Those lost to follow up were counted as continuing smokers. Where appropriate, we performed meta-analysis using a fixed-effect model. MAIN RESULTS: We identified 24 reports of studies. The only comparison for which there were sufficient studies to combine meaningfully was acupuncture compared with sham acupuncture. The fixed-effect odds ratio (OR) for the short-term effect was 1.36 (95% confidence interval 1.07 to 1.72), but the studies are heterogeneous and the result is strongly influenced by one individual positive study. The significant short-term effect was lost with the random-effects model for pooling, or by removing the outlying study that led to heterogeneity. The long-term result shows no effect of acupuncture compared with sham acupuncture. There was no consistent evidence that acupuncture is superior to no treatment, and no evidence that the effect of acupuncture was different from that of other anti-smoking interventions, or that any particular acupuncture technique is superior to other techniques. AUTHORS' CONCLUSIONS: There is no consistent evidence that acupuncture, acupressure, laser therapy or electrostimulation are effective for smoking cessation, but methodological problems mean that no firm conclusions can be drawn. Further research using frequent or continuous stimulation is justified.

Acupressure↗
PubMed2006

Post-wildfire logging hinders regeneration and increases fire risk.

We present data from a study of early conifer regeneration and fuel loads after the 2002 Biscuit Fire, Oregon, USA, with and without postfire logging. Natural conifer regeneration was abundant after the high-severity fire. Postfire logging reduced median regeneration density by 71%, significantly increased downed woody fuels, and thus increased short-term fire risk. Additional reduction of fuels is necessary for effective mitigation of fire risk. Postfire logging can be counterproductive to the goals of forest regeneration and fuel reduction.

Conservation of Natural Resources↗
PubMed2004

Characterizing gastrointestinal transit time in four lemur species using barium-impregnated polyethylene spheres (BIPS).

Differences in dietary profiles and gastrointestinal (GI) morphologies observed across lemur species suggest that there may be variation in patterns of digesta flow through the GI tract related to the method of digesta processing. Using radio-opaque barium-impregnated polyethylene spheres (BIPS), we characterized such patterns in four lemur species: Varecia variegata (VV), Eulemur fulvus (EF), Propithecus verreauxi (PV), and Hapalemur griseus (HG) (n = 2 per species). After an initial radiograph was taken under light sedation, the animals were fed the BIPS together with a small meal. A combination of 30 small (1.5 mm) and 10 large (5 mm) BIPS was administered. Radiographs were then taken on a species-dependent basis up to 48 hr post-dosage. For small BIPS, the gastric transit time (GTT; time of first exit of BIPS from stomach) was 0.25-2 hr for VV, EF, and HG, and approximately 10 hr for PV. The oro-rectal transit time (ORTT; time of first appearance in the rectum) was < 2 hr for VV and EF, and 24.0 hr for PV and HG. The intestinal transit time (ITT, measured as ORTT - GTT) was < 1.5 hr for VV and EF, and approximately 14 hr and 22 hr for PV and HG, respectively. These data suggest that the GTT of digesta as measured with BIPS was rapid for VV, EF, and HG. For VV and EF, the ORTT and ITT were also rapid, while for HG they were much slower. PV was characterized by delayed GTT, and a more rapid ITT compared to HG. Thus, patterns of flow for PV and HG, despite similar ORTT, differed in that HG emptied BIPS more rapidly and ITT was slower. The flow of BIPS did not differ for VV and EF. These data reveal new information in addition to the total tract transit time, and complement existing knowledge regarding anatomy and diet.

Animals↗
PubMed2004

Use of total dietary fiber across four lemur species (Propithecus verreauxi coquereli, Hapalemur griseus griseus, Varecia variegata, and Eulemur fulvus): does fiber type affect digestive efficiency?

In vivo digestibility and transit of two experimental diets were compared across four lemur species for which gastrointestinal morphology and preliminary data on physiology differ:Varecia variegata (VV), Eulemur fulvus (EF), Propithecus verreauxi (PV), and Hapalemur griseus (HG). Since free-ranging groups consume varied amounts of slowly fermentable insoluble fiber (IF) and rapidly fermentable soluble fiber (SF), differences in digestibility may be related to variation in the fiber types consumed. To investigate this, two diets were designed to provide 28% of dry matter (DM) as total dietary fiber (TDF). The ratio of IF/SF (g/g) differed across the diets (12.15:1 for the IF diet, and 3.76:1 for the IF/SF diet). The DM digestibility (DMD) of both diets differed across species: DMD was lower for EF and VV (approximately 56-58%), and higher for PV (72%) and HG (76%). The fiber digestibility results were as follows: TDF digestibility was similar for VV and EF (23% and 28%), higher for PV (56%), and highest for HG (66%). IF digestibility was lower for VV and EF (20% and 28%), and higher for PV and HG (53% and 62%). The transit times (TTs) of the two markers Cr and Co were similar (approximately 3.5 hr for VV and EF, 25 hr for PV, and 30 hr for HG). The mean retention times (MRTs) showed the same trend. The results from these captive groups suggest there are large differences in digestive efficiency that are likely related to the varied fiber composition of the free-ranging diet, and the amount of time the digesta are retained in the gut.

Animals↗
PubMed2003

Development of the satisfaction with inhaled asthma treatment questionnaire.

For the management of a condition such as asthma, patients should feel confident with their medication, feel that the treatment is adequate in controlling symptoms and that side-effects of the treatment are minimal. As no comprehensive instrument to measure patient satisfaction with inhaled asthma medication existed, the Satisfaction with Asthma Treatment Questionnaire was developed. The procedures that were used are described, and the initial validation and reliability tests are reported. The study involved focus group meetings, development, testing and modification of a preliminary instrument, and testing of the revised instrument using different samples of patients with asthma. Factor analysis of the 26-item questionnaire identified four domains reflecting four aspects of satisfaction: effectiveness of treatment, ease of use, medication burden, and side-effects and worries. Cronbach's alpha showed evidence of internal consistency reliability. Test/retest reliability ranged from 0.66-0.74. Interscale correlations were moderate-to-high. Significant correlations were found between domain and overall scale scores and patients' overall level of satisfaction. The Satisfaction with Asthma Treatment Questionnaire is potentially a useful instrument for gaining insight into patient satisfaction with inhaled treatment for asthma.

Administration, Inhalation↗
PubMed2002

Fecal inoculum can be used to determine the rate and extent of in vitro fermentation of dietary fiber sources across three lemur species that differ in dietary profile: Varecia variegata, Eulemur fulvus and Hapalemur griseus.

To estimate fermentative capacity among lemur species, four fiber substrates were tested across three species, Eulemur fulvus, Hapalemur griseus and Varecia variegata. The substrates, cellulose, beet pulp, citrus pulp and citrus pectin, ranged in composition from completely insoluble fiber (IF) to completely soluble fiber (SF), respectively. The lemurs consumed a nutritionally complete biscuit formulated for primates [85 g/100 g diet dry matter (DM)] and locally available produce (15 g/100 g diet DM). Feces were then collected and used to inoculate fermentation tubes prefilled with fiber substrates and an anaerobic growth medium. Dry matter disappearance (DMD), and acetate, propionate, butyrate, and total short-chain fatty acid (SCFA) production were measured in tubes subjected to 6, 12, 24 or 48 h of fermentation. Results were fitted to a logistic growth model. The maximal production (MP) time at which production or disappearance is at one-half maximum (t(50)) and the fermentation rate at 3 h were calculated. The maximal disappearance of DM differed among substrates (citrus pectin > citrus pulp > beet pulp; P < 0.0001) and species (E. fulvus > H. griseus > V. variegata; P < 0.001). V. variegata reached t(50) for acetate and total SCFA production faster than H. griseus or E. fulvus (P < 0.02). Three-hour production rates of acetate and total SCFA were also greater for V. variegata for citrus pulp and citrus pectin (P < 0.01). Few species differences were observed for beet pulp. Results provide evidence for differences in fermentative capacity and suggest that fiber solubility and fermentability should be considered when assessing the nutritional management of lemurs.

Animal Feed↗
PubMed2001

Identification of Cdc6 protein domains involved in interaction with Mcm2 protein and Cdc4 protein in budding yeast cells.

The Cdc6 protein (Cdc6p) has essential roles in regulating initiation of DNA replication. Cdc6p is recruited to origins of replication by the origin recognition complex (ORC) late in mitosis; Cdc6p in turn recruits minichromosome maintenance (Mcm) proteins to form the pre-replicative complex. Cdc6p is thought to interact with one or more Mcm proteins but this point has not yet been demonstrated. In the present study we observed that Cdc6p interacted significantly only with Mcm2p out of six Mcm proteins in yeast two-hybrid cells. Our results indicate that the interaction of Cdc6p with Mcm2p is specific, although we cannot exclude the possibility that the interaction might not be direct. In attempts to identify domains of Cdc6p important for interaction with Mcm2p, we tested interactions of various deleted versions of Cdc6p with Mcm2p and also with Cdc4p, which was previously known to interact with Cdc6p. The portion of Cdc6p from amino acid residues 51 to 394 was able to interact with Mcm2p. During the course of the studies we also discovered a previously undetected Cdc4p interaction domain between residues 51 and 394. Interestingly, when all six putative Cdc28 phosphorylation sites in Cdc6p were changed to alanine, a 6-7-fold increase in binding to Mcm2p was observed. This result suggests that unphosphorylated Cdc6p has higher affinity than phosphorylated Cdc6p for Mcm2p; this might partly explain the previous observation that Cdc6p failed to load Mcm proteins on replication origins during S phase when the cyclin-dependent protein kinase was active, thus helping to prevent the reinitiation of activated replicons.

Amino Acid Motifs↗
PubMed2001

Cloning of new members of heat shock protein HSP101 gene family in wheat (Triticum aestivum (L.) Moench) inducible by heat, dehydration, and ABA(1).

We have cloned two cDNAs, TaHSP101B and TaHSP101C, encoding two heat stress-inducible members of HSP101/ClpB family in bread wheat (Triticum aestivum (L.) Moench.). Proteins encoded by these cDNAs are highly similar at the primary sequence level and diverged from the previously reported TaHSP101 (designated TaHSP101A) both in the consensus ATP/GTP-binding region II and in the carboxy terminal region. The HSP101 gene was determined to be a single copy gene or a member of a small gene family in hexaploid wheat. Messages encoding HSP101 proteins were inducible by heat stress treatments in both wheat leaves and roots. Accumulation of the TaHSP101C mRNA was less abundant than that of TaHSP101B mRNA. We are showing for the first time that in addition to heat stress, expression of HSP101 mRNAs in wheat leaves was induced by a 2-h dehydration and a treatment with 5x10(-5)M ABA, but not affected by chilling or wounding, indicating that HSP101 proteins may be involved in both heat and drought responses in wheat.

Abscisic Acid↗
PubMed2001

Volatile general anesthetics reveal a neurobiological role for the white and brown genes of Drosophila melanogaster.

Molecular and cellular evidence argues that a heterodimer between two ABC transporters, the White protein and the Brown protein, is responsible for pumping guanine into pigment-synthesizing cells of the fruit fly, Drosophila melanogaster. Previous studies have not detected White or Brown outside pigment-synthesizing cells nor have behavioral effects of null mutants been reported, other than those that are visually dependent. Nevertheless, we show here that exposure to the volatile general anesthetic (VGA) enflurane reveals a difference in neuromuscular performance between wild-type flies and those that carry a null allele in either the white or brown gene. Specifically, in a test of climbing ability, w1118 or bw1 flies are much less affected by enflurane than are congenic controls. Altered anesthetic sensitivity is still observed when visual cues are reduced or eliminated, arguing that white and brown contribute to neural function outside the eye. This hypothesis is supported by the detection of white message in heads of flies that are genetically altered so as to lack pigment-producing cells. The w1118 or bw1 mutations also alter the response to a second VGA, halothane, albeit somewhat differently. Under some conditions, the combination of w1118 with another mutation that affects anesthesia leads to a drastically altered phenotype. We consider several ways by which diminished transport of guanine could influence neural function and anesthetic sensitivity.

ATP-Binding Cassette Transporters↗
PubMed2001

Age, gender, socioeconomic, and ethnic differences in patients' assessments of primary health care.

BACKGROUND: Patients' evaluations are an important means of measuring aspects of primary care quality such as communication and interpersonal care. This study aims to examine variations in assessments of primary care according to age, gender, socioeconomic, and ethnicity variables. METHODS: A cross sectional survey of consecutive patients attending 55 inner London practices was performed over a 2 week period using the General Practice Assessment Survey (GPAS) instrument which assesses 13 important dimensions of primary care provision. Variations in scale scores were investigated for differences relating to age, gender, socioeconomic, and ethnic status as reported by respondents. RESULTS: A total of 7692 questionnaires were returned (71% response rate). Valid information on age, gender, socioeconomic status, and ethnicity was available for 4819 out of 5496 adult respondents. Approximately half the respondents reported their ethnic group as "white" and most of the remaining respondents reported belonging to "black" or South Asian groups. Significant differences existed between groups of patients defined by age or ethnicity for most of the scale scores examined. Black, South Asian, and Chinese respondents reported lower scores (representing less favourable assessments) than white respondents; older respondents reported more favourable evaluations of care than younger respondents; and less affluent groups reported lower scores than more affluent groups for two of the 13 dimensions. There was no significant difference between gender groups with respect to assessment of primary care. Age and ethnicity were independent predictors of respondents' assessments of primary care. CONCLUSIONS: Differences exist between identifiable subgroups of the population in their assessments of primary health care measured using the GPAS instrument. This work adds to the literature on variation in healthcare experience and the potential for patient assessment of primary care. Further work is required to investigate these differences in more detail and to relate them to differences in the nature and process of primary care provision. Primary care providers need to ensure that services provided are appropriate for all patient groups within their communities.

Adolescent↗
PubMed2001

Practice size: impact on consultation length, workload, and patient assessment of care.

BACKGROUND: Variations in practice list size are known to be associated with changes in a number of markers of primary care. Few studies have addressed the issue of how single-handed and smaller practices compare with larger group practices and what might be the optimal size of a general practice. AIM: To examine variations in markers of the nature of the care being provided by practices of various size. DESIGN OF STUDY: Practice profile questionnaire survey. SETTING: A randomised sample of general practitioners (GPs) and practices from two inner-London areas, stratified according to practice size and patients attending the practice over a two-week period. METHOD: Average consultation length was calculated over 200 consecutive consultations. A patient survey using the General Practice Assessment Survey instrument was undertaken in each practice. A practice workload survey was carried out over a two-week period. These outcome measures were examined in relation to five measures of practice size based on total list size and the number of doctors providing care. RESULTS: Out of 202 pratices approached, 54 provided analysable datasets. The patient survey response rate was 7247/11,000 (66%). Smaller practices had shorter average consultation lengths and reduced practice performance scores compared with larger practices. The number of patients corrected for the number of doctors providing care was an important predictor of consultation length in group practices. Responders from smaller practices reported improved accessibility of care and receptionist performance, better continuity of care compared with larger practices, and no disadvantage in relation to 10 other dimensions of care. Practices with smaller numbers of patients per doctor had longer average consultation lengths than those with larger numbers of patients per doctor. CONCLUSION: Defining the optimal size of practice is a complex decision in which the views of doctors, patients, and health service managers may be at variance. Some markers of practice performance are related to the total number of patients cared for, but the practice size corrected for the number of available doctors gives a different perspective on the issue. An oversimplistic approach that fails to account for the views of patients as well as health professionals is likely to be disadvantageous to service planning.

Family Practice↗
PubMed2000

Subunit interactions within the Saccharomyces cerevisiae DNA polymerase epsilon (pol epsilon ) complex. Demonstration of a dimeric pol epsilon.

Saccharomyces cerevisiae DNA polymerase epsilon (pol epsilon) is essential for chromosomal replication. A major form of pol epsilon purified from yeast consists of at least four subunits: Pol2p, Dpb2p, Dpb3p, and Dpb4p. We have investigated the protein/protein interactions between these polypeptides by using expression of individual subunits in baculovirus-infected Sf9 insect cells and by using the yeast two-hybrid assay. The essential subunits, Pol2p and Dpb2p, interact directly in the absence of the other two subunits, and the C-terminal half of POL2, the only essential portion of Pol2p, is sufficient for interaction with Dpb2p. Dpb3p and Dpb4p, non-essential subunits, also interact directly with each other in the absence of the other two subunits. We propose that Pol2p.Dpb2p and Dpb3p.Dpb4p complexes interact with each other and document several interactions between individual members of the two respective complexes. We present biochemical evidence to support the proposal that pol epsilon may be dimeric in vivo. Gel filtration of the Pol2p.Dpb2p complexes reveals a novel heterotetrameric form, consisting of two heterodimers of Pol2p.Dpb2p. Dpb2p, but not Pol2p, exists as a homodimer, and thus the Pol2p dimerization may be mediated by Dpb2p. The pol2-E and pol2-F mutations that cause replication defects in vivo weaken the interaction between Pol2p and Dpb2p and also reduce dimerization of Pol2p. This suggests, but does not prove, that dimerization may also occur in vivo and be essential for DNA replication.

Animals↗
PubMed2000

The nuclease activity of the yeast DNA2 protein, which is related to the RecB-like nucleases, is essential in vivo.

Saccharomyces cerevisiae Dna2 protein is required for DNA replication and repair and is associated with multiple biochemical activities: DNA-dependent ATPase, DNA helicase, and DNA nuclease. To investigate which of these activities is important for the cellular functions of Dna2, we have identified separation of function mutations that selectively inactivate the helicase or nuclease. We describe the effect of six such mutations on ATPase, helicase, and nuclease after purification of the mutant proteins from yeast or baculovirus-infected insect cells. A mutation in the Walker A box in the C-terminal third of the protein affects helicase and ATPase but not nuclease; a mutation in the N-terminal domain (amino acid 504) affects ATPase, helicase, and nuclease. Two mutations in the N-terminal domain abolish nuclease but do not reduce helicase activity (amino acids 657 and 675) and identify the putative nuclease active site. Two mutations immediately adjacent to the proposed nuclease active site (amino acids 640 and 693) impair nuclease activity in the absence of ATP but completely abolish nuclease activity in the presence of ATP. These results suggest that, although the Dna2 helicase and nuclease activities can be independently affected by some mutations, the two activities appear to interact, and the nuclease activity is regulated in a complex manner by ATP. Physiological analysis shows that both ATPase and nuclease are important for the essential function of DNA2 in DNA replication and for its role in double-strand break repair. Four of the nuclease mutants are not only loss of function mutations but also exhibit a dominant negative phenotype.

Amino Acid Sequence↗