Biology subjects

Muhammad, R.

Publications and source records attributed to Muhammad, R..

4 recordsLinked to original sources

bioRxiv2026

CENP-B binds hairpin motifs in chromosome arms influencing gene expression

CENP-B, a centromeric protein known for its role in binding the B box sequence of centromeric DNA, has long been recognized as important, though not essential, for kinetochore attachment and chromosome segregation. Here, we identify an unexpected, non-centromeric role for CENP-B. We demonstrate that CENP-B binds to specific non-centromeric sites along chromosome arms, predominantly at promoters, and depletion of CENP-B leads to dysregulated gene expression. Binding is enriched in G2 phase cells and, importantly, occurs independently of the canonical B box motif. Instead, CENP-B binding in chromosome arms is defined by regions of negatively supercoiled DNA containing repetitive sequences, such as multiple CCAAT boxes, that are prone to forming secondary structures. Consistently, we find that CENP-B binds to hairpin DNA in vitro via its DNA binding domain. The chromosome arm binding pattern is conserved across cell types and is particularly prominent in the promoters of transcriptionally active replication-dependent histone genes. These findings reveal a previously unrecognized centromere-independent binding activity of CENP-B.

cell biology↗

bioRxiv2023

Spatial control of the APC/C ensures the rapid degradation of Cyclin B1

The proper control of mitosis depends on the ubiquitin-mediated degradation of the right mitotic regulator at the right time. This is under the control of the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase that is regulated by the Spindle Assembly Checkpoint (SAC). The Checkpoint prevents the APC/C from recognizing Cyclin B1, the essential anaphase and cytokinesis inhibitor, until all chromosomes are attached to the spindle. Once chromosomes are attached, Cyclin B1 is rapidly degraded to enable chromosome segregation and cytokinesis. We have a good understanding of how the SAC inhibits the APC/C, but relatively little is known about how the APC/C recognises Cyclin B1 as soon as the SAC is turned off. Here, by combining live cell imaging, in vitro reconstitution, biochemistry, and structural analysis by cryo-electron microscopy, we provide evidence that the rapid recognition of Cyclin B1 in metaphase requires spatial regulation of the APC/C. Using fluorescence cross correlation spectroscopy, we find that Cyclin B1 and the APC/C primarily interact at the mitotic apparatus. We further show that this is because Cyclin B1, like the APC/C, binds to nucleosomes, and identify an arginine-anchor in the N-terminus as necessary and sufficient for binding to the nucleosome. Mutating the nucleosome binding motif on Cyclin B1 reduces its interaction with APC/C and delays its degradation, and cells with the mutant, non-nucleosome-binding Cyclin B1 become aneuploid, demonstrating the physiological relevance of our findings. Together, our data demonstrate that mitotic chromosomes constitute a platform to promote the efficient interaction between Cyclin B1 and APC/C and ensure the timely degradation of Cyclin B1 and genomic stability.

cell biology↗

bioRxiv2023

Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex

Histone deacetylase complexes remove histone lysine acetylation, a key post-translational modification that activates transcription at each gene. Although these complexes are drug targets and crucial regulators of organismal physiology, their structure and mechanisms of action are largely unclear. Here, we present the first structure of a complete human SIN3B histone deacetylase holo-complex with and without a substrate mimic. Remarkably, SIN3B encircles the deacetylase and contacts its allosteric basic patch thereby stimulating catalysis. A SIN3B loop inserts into the catalytic tunnel, rearranges to accommodate the acetyl-lysine moiety and stabilises the substrate for specific deacetylation, which is guided by a substrate receptor subunit. Our findings provide a model of specificity for a main transcriptional regulator conserved from yeast to human and a resource of protein-protein interactions for future drug designs.

molecular biology↗

bioRxiv2020

Chalcid Hymenopteran parasitoid Dirhinus giffardii Silvestri proficiently disturbed house fly production

ObjectivesMan is always conscious about his health, and is well being challenged by many diseases. These diseases are directly causing hazards and most of them are transmitted through a vector. These vectors (mostly insects) have the ability to transfer / spread pathogenic organisms and that have the potential to cause severe epidemics. The house fly, Musca domestica (Diptera: Muscidae) plays a leading role in spreading more than 100 human and animal diseases. House fly is an eternal issue and mostly the management tactics rely on the use of chemicals either as spray, fumigants or baits. Unauthenticated behavior of these chemicals creates lethal effects on biological ecosystem, furthermore these measures may not be an effective options for outdoor management. For natural and safe option, bio-control strategy is being utilized to make environment healthy and clean. The present study was a part of such effort to use this strategy and validate the biological performance of the potential pupal parasitoid Dirhinus giffardii Silvestri against house fly and provide alternative and safe control of filthy flies. This is the first report on parasitism potential of D. giffardii Silvestri against house fly. ResultsThe D. giffardii Silvestri, 1913 (Hymenoptera: Chalcididae), early reported as an effective pupal parasitoid of tephritid flies, here in the case presented, showed overall 70% reduction in the house fly population by parasitizing pupae. The parasitism efficiency and longevity of hymenopteran parasitoid was remarkably noted two-fold higher on house fly pupae as compared to primary hosts (Tephritids). An amazing results were recorded on house fly parasitism, where, female production was increased one fold as compared to tephritids. Furthermore, sex ratio of the resultant progeny was also confirmed the dominancy of female by 74% as compared to males. Based on the unique and remarkable findings we therefore conclude that D. giffardii is the best bio-control agent for controlling house flies and provide healthy, clean and ecofriendly environment.

zoology↗