Hypermutation of Immunoglobulin Genes in Memory B Cells of DNA Repair–deficient Mice

To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency, distribution, and pattern of mutations in rearranged Vλ1 light chain genes from naive and memory B cells in DNA repair–deficient mutant mouse strains. Hypermutation was found unaffected in mice carrying mutations in either of the following DNA repair genes: xeroderma pigmentosum complementation group (XP)A and XPD, Cockayne syndrome complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54 (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase (AAG). These results indicate that both subpathways of nucleotide excision repair, global genome repair, and transcription-coupled repair are not required for somatic hypermutation. This appears also to be true for mismatch repair, RAD54-dependent double-strand–break repair, and AAG-mediated base excision repair

Kin17, a mouse nuclear zinc finger protein that binds preferentially to curved DNA.

Kin17 is a 45 kDa protein encoded by the KIN17 gene located on mouse chromosome 2, band A. The kin17 amino acid sequence predicts two domains, which were shown to be functional: (i) a bipartite nuclear localization signal (NLS) that can drive the protein to the cell nucleus, (ii) a bona fide zinc finger of the C2H2 type. The zinc finger is involved in kin17 binding to double-stranded DNA since a mutant deleted of the zinc finger, kin17 delta 1, showed reduced binding. Single-stranded DNA was bound poorly by kin17. Interestingly, we found that kin17 protein showed preferential binding to curved DNA from either pBR322 or synthetic oligonucleotides. Binding of kin17 to a non-curved DNA segment increased after we had inserted into it a short curved synthetic oligonucleotide. Kin17 delta 2, a mutant deleted of 110 amino acids at the C-terminal end, still exhibited preferential binding to curved DNA and so did kin17 delta 1, suggesting that a domain recognizing curved DNA is located in the protein core

Maquiavel, a república e o desejo de liberdade Maquiavel, the republic and the desire of freedom

O objetivo do artigo é compreender alguns aspectos do republicanismo de Maquiavel concedendo atenção à sua teoria dos humores. Mais especificamente, trata-se de entender qual a natureza do desejo do povo e seu papel na vida política. A principal hipótese deste trabalho é a de que a função que Maquiavel atribui ao povo, o guardião da liberdade, exige, para seu cumprimento, a participação ativa do cidadão nos afazeres cívicos, isto é, sua inscrição no espaço público como agente político. Essa inscrição não pode ser inteiramente compreendida se o desejo que caracteriza o povo carecer de qualquer determinação, isto é, se for tomado somente em uma perspectiva negativa.<br>The aim of the article is to understand some aspects of the Machiavelli's republicanism granting attention to his theory of the umori. More specifically, my purpose can be summarized as understanding the nature of the "desire of the people" and its role in the political life. The main hypothesis of this work is that the function that Machiavelli attributes to the people, the guardian of the freedom, demands, for its execution, the active participation of the citizen in the civic tasks, that is, his inscription in the public space as a political agent. That inscription cannot be understood entirely if the desire that characterizes the people lacks of any determination, that is, if it be only taken in a negative perspective