Photovoltaic (PV) technologies are a promising approach to achieve clean, renewable energy production on a global scale. However, the widespread implementation of this technology is limited due to the intricate challenges associated with its complex electrochemical processes. One such challenge is the formation of long-lived charge-separated states (CSSs), a process that directly influences device efficiencies. Viable strategies for increasing CSS lifetimes involve the inhibition of parasitic back-electron transfer pathways. In liquid-junction PVs, electronic recombination is prevented by utilizing redox electrolytes that promote directional electron transfer at the electrode/electrolyte interface, where forward electron transfer (i.e. to the electrode) is favored and the corresponding electronic recombination reaction is impeded. To meet this criterion, researchers seek to employ redox electrolytes that undergo a spin-exchange reaction induced by electron transfer. This event, known as charge transfer-induced spin crossover (CTISC), significantly increases the reorganization energy associated with electronic recombination, producing long-lived CSSs and elevated device efficiency. This dissertation describes a suite of manganese-based redox mediators that exhibit CTISC across a tunable range (1.5 V) of formal potentials (E1/2). These complexes are utilized as redox electrolytes in liquid-junction PVs and result in a two-fold enhancement in the device efficiency relative to other CTISC redox species. Photosensitizer regeneration rates are monitored using transient absorption spectroscopy (TAS) to discern the optimal E1/2 values in this class of complexes while density functional theory is employed to calculate the reorganization energy of each species. By implementing these promising electrolytes into PV devices, scientists and engineers are armed with new tools to increase the accessibility and efficiency of next-generation PVs, thereby transforming past promises into progress. / Doctor of Philosophy / To realize next-generation renewable fuels, scientists must understand how electron transfer at an interface is controlled. This dissertation highlights one method of forming a chemically useful and long-lived charge separated state. The formation of this charge separated state is achieved through an electronic reorganization that occurs at a metal center after electron transfer. Chapters 2, 3, and 4 investigate the synthesis and characterization of new metal species that possess this electronic reorganization process and provide an advanced understanding of how this process facilitates the formation of long-lived charge separated states. This work is intended to motivate new schools of thought that aid the design of next-generation catalytic materials for light-driven chemical reactions.

Yes / Bayesian statistical inference relies on the posterior distribution. Depending on the model, the posterior can be more or less difficult to derive. In recent years, there has been a lot of interest in complex settings where the likelihood is analytically intractable. In such situations, approximate Bayesian computation (ABC) provides an attractive way of carrying out Bayesian inference. For obtaining reliable posterior estimates however, it is important to keep the approximation errors small in ABC. The choice of an appropriate set of summary statistics plays a crucial role in this effort. Here, we report the development of a new algorithm that is based on least angle regression for choosing summary statistics. In two population genetic examples, the performance of the new algorithm is better than a previously proposed approach that uses partial least squares. / Higher Education Commission (HEC), College Deanship of Scientific Research, King Saud University, Riyadh Saudi Arabia - research group project RGP-VPP-280.

Electron spin relaxation and carrier recombination were investigated in gallium indium nitride arsenide (GaInNAs) multiple quantum wells, using picosecond optical pulses. Pump-probe experiments were carried out at room temperature, using pulses produced by a Ti:sapphire pumped optical parametric oscillator. The peak wavelengths of the excitonic resonances for the quantum well samples were identified using linear absorption measurements, and were found to be in the range 1.25µm-1.29µm. Carrier recombination times were measured for three samples of varying nitrogen content, and were observed to decrease from 548 to 180ps as nitrogen molar fractions were increased in the range 0.45-1.24%. Carrier recombination times were also measured for samples which had undergone a post-growth annealing process, and were found to be signicantly shorter compared to times measured for as-grown samples. Electron spin relaxation time was investigated for samples with quantum well widths in the range 5.8-8nm, and was found to increase with increasing well width, (i.e. decreasing quantum confinement energy), a trend predicted by both D'Yakonov-Kachorovskii and Elliott-Yafet models of spin relaxation in quantum wells. In a further study, longer spin relaxation times were exhibited by samples containing higher molar fractions of nitrogen, but having nominally constant quantum well width. Spin relaxation times increased from 47ps to 115ps for samples containing nitrogen concentrations in the range 0.45-1.24%. Decreases in spin relaxation time were observed in the case of those samples which had been annealed post-growth, compared to as-grown samples. Finally, all-optical polarisation switching based on spin relaxation of optically generated carriers in GaInNAs multiple quantum wells was demonstrated.

L’étude de la structure génétique des populations d’agents pathogènes à grandes échelles reste très important dans la contexte de nouvelles invasions. Puccinia striiformis f.sp. tritici (PST), responsable de la rouille jaune du blé, constitue un modèle fongique d’intérêt pour les études d’invasion étant donné sa capacité de migration et l’apparition récurrente de nouvelles souches localement. Nous avons analysé la structure des populations de PST à l’échelle mondiale, à l’aide de marqueurs microsatellites sur un échantillon de 409 isolats issus des six continents. Les génotypes ont été répartis en six groupes génétiques correspondant à leur origine géographique. Les analyses indiquent une forte hétérogénéité géographique de diversité génotypique, avec des signatures de recombinaison dans les régions de l'Himalaya (Népal et Pakistan) et à proximité en Chine. La structure reste clonale pour les populations des autres régions. L’assignation des isolats aux différents groupes génétiques a permis de déterminer l’origine des invasions (récentes ou anciennes). Ainsi, les souches agressives adaptées à de hautes températures, répandues de par le monde depuis 2000, sont originaires de Mer rouge-Moyen Orient ; les isolats d'Amérique du Nord et du Sud et d’Australie proviennent d’Europe du Nord-Ouest. Par ailleurs, les isolats d'Afrique du Sud appartiennent au groupe génétique de la zone méditerranéenne. La subdivision marquée entre les différentes zones géographiques indique qu’elles ne sont pas fortement marquées par les migrations récentes. De plus, les voies de migration identifiées attestent de l'importance des activités humaines dans la dispersion de PST à longue distance. La biologie des populations des zones les plus diverses (Chine et Pakistan) a été finement étudiée à l’aide d‘échantillonnages réalisés deux années consécutives. Une population échantillonnée en 2004 et 2005 dans la vallée de Tianshui, (province de Gansu, Chine), s’est révélée très diverse, fortement recombinante et non structurée spatialement et temporellement. L’observation de clones identiques entre les deux échantillons temporels a permis de développer un estimateur du taux de sexualité, i.e. du rôle relatif de la reproduction sexuée par rapport à celui de la reproduction asexuée dans le maintien de la population. Ce taux de reproduction sexuée est estimé à 74 %, alors que la taille efficace de la population est de 1735, ce qui donne les premières indications du rôle du cycle sexué. L’échantillonnage réalisé au Nord du Pakistan a permis de décrire quatre groupes génétiques ayant tous une grande diversité génotypique et une structure recombinante. Le très faible taux de ré-échantillonnage de génotypes identiques au cours de deux années suggère le rôle prédominant de la reproduction sexuée dans le maintien temporel des populations locales. La forte diversité génétique et génotypique, la signature de recombinaison et la capacité à la reproduction sexuée de PST dans la région himalayenne suggèrent que cette zone est le centre d'origine potentielle de PST. Les analyses d’approximations bayésiennes confirment la thèse d’une dispersion à partir de l’Himalaya vers les autres régions du monde. La variabilité pour la capacité à produire des téleutosores, spores indispensables à l’initiation de la phase sexuée, a été analysée (56 isolats mondiaux), et s’avère liée à la variabilité génotypique et au taux de recombinaison. Ce résultat conforte la thèse de l'apparition de la sexualité dans la zone himalayenne et à proximité de cette zone et de la perte de sexualité lors de migrations dans les zones où l’hôte alternant est absent et où le cycle épidémique est essentiellement asexué. La description de l'origine, des voies mondiale de migration de PST ainsi que de son centre de diversité contribue à la compréhension du potentiel évolutif de PST et à la construction de stratégies de gestion de lutte contre l’agent pathogène. / Analyses of the large-scale population structure of pathogens enable the identification of migration patterns, diversity reservoirs or longevity of populations, the understanding of current evolutionary trajectories and the anticipation of future ones. A detailed analysis of populations in centre of diversity should enable to infer the adaptive capacity of the pathogen and identify potential sources for new invasions. Puccinia striiformis f.sp. tritici (PST) is the causal agent of wheat yellow/stripe rust, and despite a worldwide distribution, this fungus remains a model species for invasion studies, due to its long-distance migration capacity and recurrent local emergence of new strains. Little is known about the ancestral relationship of the worldwide PST population with unknown center of origin. We used multilocus microsatellite genotyping to infer the worldwide population structure of PST and the origin of new invasions, analysing a set of isolates representative of sampling performed over six continents. Bayesian and multivariate clustering methods partitioned the isolates into six distinct genetic groups, corresponding to distinct geographic areas. The assignment analysis confirmed the Middle East-Red Sea Area as the most likely source of newly spreading, high-temperature-adapted strains; Europe as the source of South American, North American and Australian populations; and Mediterranean-Central Asian populations as the origin of South African populations. The existence of strong population subdivision at worldwide level shows that major genetic groups are not markedly affected by recent dispersal events. However, the sources for recent invasions and the migration routes identified emphasize the importance of human activities on the recent long-distance spread of the disease. The analyses of linkage disequilibrium and genotypic diversity indicated a strong regional heterogeneity in levels of recombination, with clear signatures of recombination in the Himalayan (Nepal and Pakistan) and near-Himalayan (China) regions and a predominant clonal population structure in other regions. To explain the variability in diversity and recombination of worldwide PST populations, we assessed their sex ability in terms of telial production, the sex-specific structures that are obligatory for PST sexual cycle, in a set of 56 isolates representative of these worldwide geographical origins. We confirmed that the variability in genotypic diversity/ recombination was linked with the sex ability, pinpointing the Himalayan region as the possible center of origin of PST, from where it then spread worldwide. The reduced sex ability in clonal populations certainly reflects a loss of sexual function, associated to migration in areas where sexual alternate host is lacking, or not necessary for the completion of epidemic cycle. Approximate Bayesian computation analyses confirmed an out of Himalaya spread of PST, with Pakistan and China being the most ancestral population. A detailed analysis of Pakistani population at regional level revealed the existence of a strong population subdivision, a high genotypic diversity and the existence of recombination signature at each location reflecting the role of sexual recombination in the temporal maintenance at local level. A time spaced sampling of PST in the valley of Tianshui (China) inspired the development of a new estimator, allowing to quantify the relative contribution of sexual reproduction and effective population size on the basis of clonal resampling within and between years. A sexual reproduction rate of 74% (95% confidence interval [CI]: 38-95%) and effective population size of 1735 (95% CI: 675-2800) was quantified in Chinese PST population. The description of the origin and migration routes of PST populations worldwide and at its centre of diversity contributes to our understanding of PST evolutionary potential, and is helpful to build disease management strategies.

Thesis (Ph. D.)--University of Missouri--Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 98-104). Also available on the Internet.

Electron-ion recombination and ion-neutral interactions play a piv- otal role in the chemical evolution of molecules in the Interstellar Medium (ISM). Physical conditions under which these processes un- dergo in the ISM include a wide range of temperatures and particle number densities. This work contributes to the experimental study of named low temperature phenomena in the range of 30 K to 300 K focusing on the reactions of hydrogen-containing light molecules. The employed experimental techniques are based on a combination of a Stationary Afterglow (SA) instrument with a Continuous Wave Cavity Ring-down Spectrometer (cw-CRDS). The main contributions of this work can be split into three topics. (1) The proton and deuteron con- taining isotopic system of H3 + ions. The isotopic fractionation process in collisions with hydrogen and deuterium gas was investigated in low temperature discharges, nominal ion temperatures of 80 K to 140 K, to deduce relative ion densities in the experiments. These are necessary for afterglow studies of isotopic effects in electron-ion recombination of the studied ions. (2) Vibrational spectroscopy of N2H+ ions focusing on first overtone (2ν1 band) transitions and ion thermometry, the first step towards studies of electron-ion recombination. (3) The role of para/ortho spin...

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京都大学 / 新制・課程博士 / 博士(医学) / 甲第25491号 / 医博第5091号 / 新制||医||1073(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 浅野 雅秀, 教授 篠原 隆司, 教授 近藤 玄 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

La rencontre des lymphocytes B matures avec l’antigène (Ag), au niveau des organes lymphoïdes secondaires, déclenche la maturation terminale, au cours de laquelle deux évènements peuvent avoir lieu : la commutation de classe de l’immunoglobuline (CSR pour Class Switch Recombination) et l’hypermutation somatique (SHM).Dernièrement, notre laboratoire a décrit pour la première fois la recombinaison suicide du locus IgH (LSR pour Locus Suicide Recombination) (Péron et al., 2012). Cette recombinaison engendre une délétion totale de l’ensemble des gènes constants du locus IgH, empêchant ainsi l’expression d’Ig, et donc l’absence du récepteur BCR (B Cell Receptor). La cellule B se retrouve privée des signaux de survie délivrés par ce récepteur, et est induite à l’apoptose. La LSR semble opérer par les mêmes étapes que la CSR : 1- la transcription de régions de l’ADN ciblées, 2- la génération de cassures double brin (CDB) à partir de lésions introduites par AID (Activation-induced cytidine deaminase), 3- la réparation de l’ADN lésé majoritairement par le système classique de ligation des extrémités non homologues (C-NHEJ). Cependant, la réparation au cours de la LSR n’a pas été pleinement décrite, et sa détermination constitue l’objectif principale de mon doctorat. Dans un premier temps, nous avons mis au point un programme bio-informatique « CSReport », afin d’analyser la masse de données générées par le séquençage haut débit de jonctions du locus IgH (CSR et LSR) (Boyer et al., 2017). Cet outil nous a permis d’étudier le système de réparation des CDB, à travers la détermination de la structure au point de jonction. De façon inattendue, nos résultats montrent que la réparation de l’ADN dans la LSR est similaire entre la souris et l’Homme et si la CSR fait intervenir le C-NHEJ, la LSR semble faire appel à l’A-EJ (Alternative End Joining) et/ou la HR (Homologous Recombination). Ces observations sont renforcées par les résultats mettant en évidence une différence de l’association de protéines de réparation, ainsi que des marques épigénétiques particulières entre les segments concernés par la CSR et ceux ciblés par la LSR chez la souris.Nous nous sommes ensuite interrogés sur la LSR dans le lymphome de Hodgkin (HL pour Hodgkin lymphoma), car l’absence de BCR à la surface des cellules de Reed Sternberg pourrait provenir de cet évènement. Les résultats de séquençage haut débit révèlent une réparation différente au cours de la LSR entre le HL et le contrôle (amygdales saines) ce qui nous laisser stipuler que des altérations intrinsèques aux systèmes de réparation de l’ADN dans les cellules tumorales sont en cause.Globalement, nous avons développé « CSReport », un outil qui nous permet d’analyser la structure de réparation de l’ADN en partie, et de montrer une réparation similaire des CDB entre la souris et l’Homme et une différence de réparation de l’ADN entre la recombinaison CSR et LSR. De plus, nous avons mis en évidence une altération de la réparation dans des échantillons de lymphomes B (HL et CLL) comparé à des contrôles (amygdales saines). / Mature B lymphocytes meeting with antigen (Ag) inside secondary lymphoid organs activates their terminal maturation, with occurrence of class switch recombination (CSR) and somatic hyper mutation (SHM).Recently, our laboratory described for the first time IgH locus suicide recombination (LSR) (Péron et al., 2012). This process removes the whole constant genes of the locus, preventing Ig and BCR (B Cell Receptor) expression. The B cell is devoid of survival signals delivered by its receptor and is induced to apoptosis.LSR seems to operate with same molecular steps as CSR : 1- transcription of targeted DNA regions, 2- generation of double strand breaks (DSB) from DNA lesions induced by AID (Activation-induced cytidine deaminase), 3- DNA repair by classical non homologous end joining (C-NHEJ) pathway. However, DNA repair during LSR was not fully understood, and this is the principal objectif of my PhD studies. First, we developped a bioinformatic program « CSReport », to analyse high throughput sequencing (HTS) datas of IgH locus junctions (CSR and LSR) (Boyer, Boutouil et al.,2017). This tool allowed us to study the DSB repair systems, through determination of the structure at the junction site. Unexpectedly, our results show that DNA repair in DNA during LSR is similar between mice and human, and if CSR implicates C-NHEJ, LSR seems to invlove Alternative end joining (A-EJ) and /or homologous recombination (HR). These observations are consolidated by results showing a difference in the association of repair proteins, and in particular epigenitic marks between DNA segments concerned by CSR and those targeted by LSR in mice. We asked ourselves about LSR in HL, because BCR absence on its Reed Sternberg cells surface may be a result of this recombination. HTS results reveal a different repair during LSR between HL and the control (healthy tonsils), which let us stipulate that alterations in DNA repair systems of tumoral cells are the cause.Globaly, we developped « CSReport », a tool which permits us to study DNA repair structure in a part, and to show a similar DSB repair systems between mice and human, and a difference between CSR and LSR repair. Furthermore, we show an alteration in DNA repair of B lymphoma samples (HL and CLL) compared with the control (healthy tonsils).

Homologous genetic recombination, because of its fundamental roles in the maintenance of genome stability and evolution, is an essential cellular function common to all organisms. This process also plays important roles in the repair of damaged DNA molecules, generation of genetic diversity and proper segregation of chromosomes. The genetic exchange is a highly orchestrated process that entails a plethora of control mechanisms and a large number of proteins, of which RecA and SSB are two proteins that have been chosen for further investigation(s) in the present study. In addition, we have also investigated the interaction between SSB and UvrD1, which plays an important role in DNA repair pathways, especially nucleotide excision repair (NER) and mismatch repair as well as DNA replication and recombination. Chapter 1 reviews the literature regarding various aspects of homologous recombination, with an emphasis on the biochemical and the biophysical aspects of RecA and SSB proteins. In addition, it provides an overview of the study of DNA repair and recombination in mycobacteria. RecA protein is ubiquitous and well conserved among bacterial species. Many archaeal species possess two RecA homologues (RadA and RadB) and eukarya possess multiple homologues of RecA including, Rad51, Rad51B, Rad51C, Rad51D, DMC1, XRCC2, or XRCC3. RecA or its homologues function as polymers, consisting of hundreds of monomers that cooperatively polymerize on single-stranded DNA to form a nucleoprotein filament. E. coli RecA protein participates in Trans Lesion Synthesis (TLS) of DNA and forms the minimal mutasome in association with DNA polymerase V (UmuD’2C). The fundamental mechanism underlying HR, i.e. DNA strand exchange, is one of the most fascinating examples of molecular recognition and exchange between biological macromolecules. Since the isolation of E. coli recA gene and the subsequent purification of its gene product and also from other organisms, RecA protein has been studied extensively for more than three decades. E. coli RecA protein has pivotal roles in DNA recombination and repair, and binding to DNA in the presence of ATP, is a fundamental property of RecA protein resulting in the formation of a nucleoprotein filament. This is the slow step of the HR process, and is considerably faster on ssDNA than on duplex DNA. Binding of RecA to dsDNA is slower at physiological pH, is accelerated at acidic pH, and the lag in binding at the higher pH values is due to slow nucleation. The ATP and the DNA binding functions of RecA display allosteric interaction such that ATP- binding leads to an increase in affinity to ssDNA-binding and vice-versa. X-ray structures of E. coli RecA complexed with nucleotide cofactors have implicated a highly conserved Gln196 in Mycobacterium smegmatis RecA in the coupling of ATP and the DNA binding domains. The carboxyamide group of Gln196 makes an H-bond with the γ-phosphate group of ATP and the side chain of this residue is observed to move by approximately 2Å towards the ATP, relative to the other residues involved in ATP binding. In addition, a highly conserved Arg198 has also been postulated to interact with the γ-phosphate group of bound ATP and position it for a nucleophilic attack by a conserved residue-Glu96 leading to ATP hydrolyses. To elucidate the role of Gln196 and Arg198 in the allosteric modulation of RecA functions, we generated MsRecA variant proteins, where in Gln196 was substituted with alanine, asparagine or glutamate; Arg198 was mutated to a lysine. The biochemical characterization of MsRecA and its variant proteins with the objective of defining the allosteric interaction between the ATP- and the DNA-binding sites has been described with in Chapter 2. We observed that while the mutant MsRecA proteins were proficient in ATP-binding they were deficient in ATP hydrolyses. We assayed for the ability of these proteins to bind ssDNA using either nitrocellulose filter binding or Surface Plasmon Resonance (SPR). While we did not detect any ssDNA-binding by the mutant MsRecA proteins in the filter binding assay, we observed only ten-fold reduction in the affinity for ssDNA as compared to wild type MsRecA protein in MsRecAQ196A, Q196N and R198K in the SPR assay. MsRecA Q196E did not show any binding to ssDNA, in both nitrocellulose filter-binding as well as SPR assays. We assayed for the ability of the mutant RecA proteins for their ability to promote DNA-pairing as well as DNA strand exchange. While we observed limited pairing promoted by the mutant proteins relative to the wild-type MsRecA, we observed a complete abrogation of strand exchange in the case of mutant proteins. In addition, we assayed for the co-protease function of MsRecA, by monitoring the cleavage of MtLexA. We observed that only the wild-type MsRecA protein was able to cleave MtLexA, while none of the mutant RecA proteins were able to do so. In order to understand the differences observed between the wild -type and the mutant MsRecA proteins, we analyzed the conformational state of MsRecA and its variant proteins by circular dichroism spectroscopy upon ATP-binding. We observed that while MsRecA and MsRecAQ196N displayed a reduction in the absorbance at 220 nm upon ATP binding, we did not observe any such structural transitions in the other mutant MsRecA proteins that we tested. Based on our observations and the crystal structure of E. coli RecA bound to ssDNA, in Chapter 2, we propose a dual role for the Gln196 and Arg198 in modulating RecA activities. In the presynaptic filament Gln196 and Arg198 sense the presence of the nucleotide in the nucleotide binding pocket and initiate a series of conformation changes that culminate in the transition to an active RecA nucleoprotein filament. In the active RecA nucleoprotein filament these residues are repositioned such that they now form a part of the protomer-protomer interface. As such they perform two vital functions; they stabilize the protomer-protomer interface by participating in the formation of hydrogen bonds that span the interface as well transmit the wave of ATP hydrolysis across the interface leading to a coordinated hydrolyses of ATP essential for the heteroduplex extension phase of strand exchange reaction. The members of the super family of single stranded DNA binding proteins (SSB) play an important role in all aspects of DNA metabolism including DNA replication, repair, transcription and recombination. Prokaryotic SSBs bind ssDNA with high affinity and generally with positive cooperativity. Several lines of evidence suggest that prokaryotic SSBs are modularly organized into three distinct domains: the N-terminal DNA binding domain and acidic C-terminal domain are linked by a flexible spacer. Studies from our laboratory have revealed that M. smegmatis SSB plays a concerted role in recombination-like activities promoted by the cognate RecA. The C- terminal of SSB is known to be involved in its ability to interact with other proteins. We have previously reported that the C-terminal domain of M. smegmatis SSB, which is not essential for interaction with DNA, is the site for the binding of cognate RecA. The data in Chapter 3 describes the characterization of the SSB C-terminus with the objective of delineating the elements responsible for mediating protein-protein interaction, as well as to define the mechanism by which SSB is able to modulate the activities of RecA. To map the RecA interaction domain of SSB we created deletion mutants in MsSSB lacking 5, 10, 15 or 20 residues from the C-terminal. The truncated SSB proteins were expressed with a His- tag at the N- terminus and purified to homogeneity using a Ni-NTA affinity matrix. We observed unlike MsSSB, MsSSB∆C5 and MsSSB∆C10, MsSSB∆C15 and MsSSB∆C20 were unable to support three-strand exchange catalyzed by MsRecA. Based on the observation that interaction with SSB is essential for MsRecA to catalyze the strand Exchange reaction, we postulate that the RecA interacting domain of SSB is situated between the 15th and the 20th residue from the C-terminal. Further, the C-terminal of MsSSB modulates the transitions between DNA binding modes. Unlike the case with EcSSB where deletion of the last 8 residues from the C-terminal stabilizes the (SSB)35 mode of ssDNA binding, we observe that in case of MsSSB the deletion of C-terminal seems to destabilize the (SSB)35. In addition, the transition from the low density binding mode to a high density mode involves the formation of several intermediates when the C-terminal residues are deleted. With the objective of understanding the functions to the C-terminal of SSB independent of its DNA-binding domain in modulating RecA functions, we employed a peptide corresponding to the 35 residues from the C-terminal of the MsSSB. We observed that the C-terminal region alone is capable of interacting with RecA. In addition we also observed that the C-terminal domain of SSB stimulates RecA functions independent of its DNA binding domain. To address the question, whether the stimulatory effect of the C-terminal domain of SSB in the absence of its DNA-binding domain is restricted to RecA or is a generalized phenomenon associated with all SSB interacting proteins; we tested the effect of C-terminal domain of SSB on UvrD which is known to interact with SSB. UvrD participates in several pathways of DNA metabolism, which include the nucleotide excision repair (NER) and mismatch repair pathway, replication and recombination. Genetic evidence suggests that UvrD and SSB interact in vivo. We tested the effect of mycobacterial SSB on M. tuberculosis UvrD1 (MtUvrD1) functions in vitro. We observe that MtUvrd1 physically interacts with SSB. Further, presence of SSB has an inhibitory effect on the helicase activity of MtUvrD1 and that this effect is dependent on the C-terminal region as the deletion of residues from the C-terminal of SSB abrogates the inhibitory effect of SSB. However, unlike RecA, the C-terminal region of SSB alone had no effect on the helicase activity of UvrD1. We also observed that MsSSB has opposing effects on the ATPase activity of MtUvrD1. In the presence of low concentrations of SSB the ATPase activity is enhanced, while we observed an inhibition when the concentration of MsSSB is high. The precise mechanistic details of how SSB is able to act as an accessory protein to RecA, in context of homologous recombination and stimulates its biochemical activities have been a subject of debate. Whereas research from some groups has shown that the stimulatory effect SSB is mediated through its ability to melt DNA secondary structure, thereby allowing RecA to overcome the kinetic barrier imposed by the presence of secondary structure in ssDNA, others postulate that SSB plays a direct role in the stabilization of RecA nucleoprotein filament and prevents its dissociation. Chapter 3 discusses the experimental evidence in favor of the aforesaid models and based on the results of our experiments; we propose that the accessory functions of SSB may be mediated by a mechanism that involves elements of both models. While interaction with SSB can bring about a conformational change in RecA that is reflected in the enhanced levels of strand exchange and co-protease activity, the helix destabilizing function of SSB is essential during heteroduplex extension and to sequester the displaced strand such that it does not participate in any further pairing reactions. The novel finding that we present in Chapter 3 is that the interaction of SSB C-terminal alone has a stimulatory effect upon RecA activities. Furthermore, we observed that M. tuberculosis UvrD1 is a weak interaction partner of SSB. The physical and functional interactions between MsSSB with RecA on the one hand, and MsSSB and UvrD1 on the other highlight different types of cross-talk between the components of HR and DNA repair pathways. In contrast to the results of earlier studies, our results indicate that protein-protein interactions alone between SSB and RecA may modulate the RecA mediated processes of presynapsis, homologous pairing and strand exchange between homologous DNA molecules as well as modulate its co-protease activity. In addition, our studies indicate that a direct protein-protein interaction is responsible for the modulation of UvrD1 activities by SSB.