RESUMO
Replication protein A-1 (RPA-1) is a single-stranded DNA-binding protein involved in DNA metabolism. We previously demonstrated the interaction between LaRPA-1 and telomeric DNA. Here, we expressed and purified truncated mutants of LaRPA-1 and used circular dichroism measurements and molecular dynamics simulations to demonstrate that the tertiary structure of LaRPA-1 differs from human and yeast RPA-1. LaRPA-1 interacts with telomeric ssDNA via its N-terminal OB-fold domain, whereas RPA from higher eukaryotes show different binding modes to ssDNA. Our results show that LaRPA-1 is evolutionary distinct from other RPA-1 proteins and can potentially be used for targeting trypanosomatid telomeres.
Assuntos
DNA de Cadeia Simples/metabolismo , Leishmania , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Proteína de Replicação A/química , Proteína de Replicação A/metabolismo , Telômero/genética , Sequência de Aminoácidos , Simulação por Computador , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Oligonucleotídeos/metabolismo , Oligossacarídeos/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Especificidade da EspécieRESUMO
Abnormal Papanicolaou smears has increased in adolescents. Our objective was to analyze the frequency of cervical intraepithelial neoplasia (CIN) in adolescents (< 20 years of age) over the last 12 years, comparing to adult (> or = 20 years of age). We studied 110,283 (10.85% of adolescents) reports from Papanicolaou smears between 1987 and 1999 in a public university hospital that has a screening program for cervical cancer prevention. The tests were divided into 3 periods (1987-1991, 1992-1995 and 1996-1999) for studying the evolution of frequencies. CIN I was more frequent among adolescents (1.73% vs. 0.99%) and CIN III and invasive cancer among adult women (0.62% vs. 0.05%, and 0.39% vs. 0.0083%, respectively). Between the periods 1987-1991 and 1996-1999 there was an increased in the frequency of CIN I among adolescents (from 0.78-2.17%) and adults (from 0.72-1.16%); CIN II decreased among adult patients (from 0.52-0.28%) and tripled among adolescents over recent years (from 0.15-0.47%), and CIN III increased in both group, although without statistical significance. One case of invasive carcinoma among adolescents occurred in the period from 1996-1999. We strongly recommend the inclusion of adolescent populations in the screening programs, from the time that they begin sexual activity.