Biology subjects

Rawal, C.

Publications and source records attributed to Rawal, C..

3 recordsLinked to original sources

bioRxiv2019

Rad9/53BP1 promotes crossover recombination DNA repair by limiting the Sgs1 and Mph1 helicases

A DNA double strand break (DSB) is primed for homologous recombination (HR) repair through the nucleolytic processing (resection) of its ends, leading to the formation of a 3' single-stranded DNA (ssDNA). Generation of the ssDNA is accompanied by the loading of several repair factors, including the ssDNA binding factor RPA and the recombinase Rad51. Then, depending upon the availability and location of a homologous sequence, different types of HR mechanisms can occur. Inefficient or slow HR repair results in the activation of the DNA damage checkpoint (DDC)1. In budding yeast, the 53BP1 ortholog Rad9 acts as a scaffold, mediating signal from upstream kinases Mec1 and Tel1 (ATR and ATM in human) to downstream effectors kinases Rad53 and Chk1 (CHK2 and CHK1 in human). In addition to its role in DDC, Rad9 limits DSB resection 2. Remarkably, this function is conserved in 53BP1, also being implicated in cancer biology in human cells 3,4.\n\nHere we show that Rad9 limits the recruitment of the helicases Sgs1 and Mph1 on to a DSB, promoting Rad51-dependent recombination with long track DNA conversions, crossovers and break-induced replication (BIR). This regulation couples the DDC with the choice and effectiveness of HR sub-pathways, and might be critical to limit genome instability with implication for cancer research.

molecular biology↗

bioRxiv2017

A synergistic transcriptional regulation of olfactory genes derives complex behavioral responses in the mosquito Anopheles culicifacies

Decoding the molecular basis of host seeking and blood feeding behavioral evolution/adaptation in the adult female mosquito may provide an opportunity to design new molecular strategy to disrupt human-mosquito interactions. However, despite the great progress in the field of mosquito olfaction and chemo-detection, little is known that how the sex-specific specialization of the olfactory system enables adult female mosquitoes to derive and manage complex blood feeding associated behavioral responses. A comprehensive RNAseq analysis of prior and post blood meal olfactory system of An. culicifacies mosquito revealed that a minor but unique change in the nature and regulation of key olfactory genes play a pivotal role in managing diverse behavioral responses. Age dependent transcriptional profiling demonstrated that adult female mosquitos chemosensory system gradually learned and matured to drive the host-seeking and blood feeding behavior at the age of 5-6 days. A zeitgeber time scale expression analysis of Odorant Binding Proteins (OBPs) unravels unique association with a late evening to midnight peak biting time. Blood meal-induced switching of unique sets of OBP genes and Odorant Receptors (ORs) expression coincides with the change in the innate physiological status of the mosquitoes. Blood meal follows up experiments provide enough evidence that how a synergistic and concurrent action of OBPs-ORs may drive prior and post blood meal complex behavioral events. Finally, tissue-specific gene expression analysis and molecular modelling predicted two uncharacterized novel sensory appendages proteins (SAP-1 & SAP2) unique to An. culicifacies mosquito and may play a central role in the host-seeking behavior.\n\nSignificanceEvolution and adaptation of blood feeding behavior not only favored the reproductive success of adult female mosquito but also make them an important disease vectors. Immediately after emergence, an environmental exposure may favor the broadly tuned olfactory system of mosquitoes to derive complex behavioral responses. But, how these olfactory derived genetic factors manage female specific pre and post blood meal associated complex behavioral responses are not well known. We unraveled synergistic actions of olfactory factors governs an innate to prime learning strategy to facilitate rapid blood meal acquisition and downstream behavioral activities. A species-specific transcriptional profiling and an in-silico analysis predict novel sensory appendages protein, as a unique target to design disorientation strategy against the mosquito Anopheles culicifacies.

animal behavior and cognition↗

bioRxiv2017

Sex Specific Molecular Responses Of Quick-To-Court In Indian Malarial Vector Anopheles culicifacies: Conflict Of Mating And/Or Blood Feeding?

Understanding the molecular basis of mosquito behavioral complexity is central to the design of novel molecular tool to fight against their vector borne diseases. Although, olfactory system play important role to guide and manage many behavioral co-ordinates including feeding, mating, breeding etc., but the sex specific regulation of olfactory responses remains unanswered. From our ongoing transcriptomic data annotation of blood fed adult female olfactory tissue of A. culicifacies mosquito, we identified a 383 bp long unique transcript encoding Drosophila homolog of Quick-To-Court protein, previously shown to regulate the courtship behavior in adult male Drosophila. A comprehensive in silico analysis predicts Ac-qtc is 1536 bp long single copy gene encoding 511 AA long protein, having high degree of conservation with other insect homolog. Age dependent increased expression of putative Ac-qtc in the naive mosquitoes correlates the maturation of olfactory system, necessary to meet sex specific conflicting demand of mating (mate finding) vs. host-seeking behavioral responses. Though, 16-18 hour of starvation did not altered Ac-qtc expression in both the sexes, however blood feeding significantly modulated its response in the adult female mosquitoes, confirming that it may not be involved in sugar feeding associated behavioural regulation. Finally, a behavioural-cum-molecular assay indicated that natural dysregulation of Ac-qtc in late evening may promotes key mating event of successful insemination process. We hypothesize that Ac-qtc may play unique role to meet and manage the sex specific conflicting demand of mosquito courtship behaviour and/or blood feeding behaviour in the adult female mosquitoes. A molecular mechanism elucidation may provide new knowledge to consider Ac-qtc as a key molecular target for mosquito borne disease management.

animal behavior and cognition↗