In many eubacteria, coexpression of recX with recA is essential for attenuation of the deleterious effects of recA overexpression; however, the molecular mechanism has remained enigmatic. Here T he past several years have seen a considerable progress in our understanding of the central role of Escherichia coli RecA protein in homologous recombination, DNA repair, restoration of stalled replication forks, induction of SOS response, and mutagenesis (1, 2). The much-studied homologous recombination process in vitro is the three-strand exchange reaction between circular single-and linear double-stranded DNA (1-3). In this model, the reaction proceeds in three sequential phases: (i) The presynaptic polymerization of RecA protein on singlestranded DNA; (ii) synapsis, the homologous alignment of nucleoprotein filament with linear double-stranded DNA; and (iii) unidirectional strand exchange (1-3). The mechanistic aspects of homologous recombination promoted by the prototype E. coli RecA protein may arguably be the best understood, but understanding its counterparts from other organisms will be essential to establish the generality of the phenomenon. To this end, we have described the biochemical characterization and x-ray structure of M. tuberculosis RecA (4-6).In some eubacteria, recX is located on the same coding strand downstream of recA (7). In Streptomyces lividans, Mycobacterium smegmatis, Mycobacterium tuberculosis, Pseudomonas aeruginosa, or Thiobacillus ferrooxidans, the ORFs of recA and recX overlap and the two genes are cotranscribed (7-12). It is known that overexpression of recA in recX mutants of S. lividans, M. smegmatis, or P. aeruginosa, but not mutant RecA, lead to induction of deleterious effects (8, 10, 13). However, the molecular mechanisms by which recX attenuates the deleterious effects induced by recA overexpression has remained unknown. Using M. tuberculosis as a model, we explored the mechanism by which RecA is regulated by RecX. Here, we show that RecX interacts directly with RecA in vitro and in vivo resulting in suppression of ATPase and strand exchange, processes that are central to homologous recombination. The negative regulation of RecA by RecX implies that RecX might act as an antirecombinase to quell inappropriate recombinational repair during normal DNA metabolism. (14) and their concentrations determined as described (15). Negatively supercoiled (form I) and circular single-stranded M13 DNA (ssDNA) was prepared as described (16). The concentrations are expressed in moles of nucleotide residues. Materials and Methods Purification of RecX. E. coli BL21(DE3)[pLysS] strain harboringM. tuberculosis recX gene on plasmid pET15b was cultured in 1 liter of LB medium containing 50 g͞ml ampicillin and 34 g͞ml chloramphenicol at 37°C. At mid-exponential phase (A 600 ϭ 0.4), recX expression was induced by adding isopropyl ␤-Dthiogalactoside (IPTG) to a final concentration of 0.5 mM and incubated for 4 h. All subsequent steps were performed at 4°C unless indicated otherwise. Cell paste (8 g) was...

There is compelling evidence that patients with schizophrenia are prone to gain weight. In addition, atypical antipsychotic (AAP) drugs also induce weight gain. All antipsychotic drugs produce weight gain but the potential varies. Many studies overwhelmingly confirm that AAP drugs produce substantially more weight gain in comparison to conventional antipsychotic drugs. Clozapine and olanzapine have the most weight inducing potential. Even ziprasidone, which is considered to be weight neutral, and aripiprazole a dopamine modulator produce weight gain in some. The pathophysiology of weight gain is complicated. Many neurohormones, neuropeptides, gut hormones, as well as adipose tissue and hair root derived hormones interact with environmental factors to produce weight gain. Management of weight gain is a difficult problem. Basic to treatment is an understanding of the etiology. Drug induced obesity provides a unique opportunity to psychiatrists to understand this clinically important problem. In the absence of this knowledge, prevention is the best hope. Education, diet control and simple behavioral measures may prevent excessive weight gain. In those with weight gain, treatment can be attempted with pharmacotherapy with careful monitoring of the side effects.

Recently, there has been increased concern about the occurrence of diabetes associated with the use of atypical antipsychotic (AAP) drugs. The relationship between diabetes, schizophrenia, and antipsychotic drugs is complex and intriguing, as untreated patients with schizophrenia are known to suffer from diabetes more often than the general population. Thirty individual case reports of clozapine-, 26 cases of olanzapine- and a few others of seroquel- and risperidone-associated diabetes mellitus, hyperglycemia and diabetic ketoacidosis were found by a Medline search. The case reports do not provide the incidence of diabetes in patients treated with AAP drugs, but they suggest that AAP drugs may cause hyperglycemia. Further research is needed to identify the cause of the susceptibility of the schizophrenic population, and to elucidate the mechanisms by which the antipsychotic drugs either cause diabetes or precipitate its onset. Which antipsychotic drugs have a higher and which have a lower potential to induce diabetes is not conclusively answered at present. However, the findings that 50% of the patients completely improve upon drug discontinuation, and that hyperglycemia promptly recurs upon reinstitution of the incriminated drug indicate that this side effect is reversible and is drug related. African Americans are particularly susceptible to AAP drug-induced diabetes. Until the new research data become available, AAP drug treatment of schizophrenic patients aims at prevention, institution of vigilant screening procedures, and management of hyperglycemia.