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Biology subjects

Leong, S. L.

Publications and source records attributed to Leong, S. L..

2 recordsLinked to original sources

S. pombe Mto1:Mto2 stabilizes γ-tubulin positions within the γ-TuRC

Microtubules are present in all eukaryotes and are nucleated by multiprotein {gamma}-tubulin ring complexes ({gamma}-TuRCs), ring-shaped structures that contain several copies of the {gamma}-tubulin small complex ({gamma}-TuSC). {gamma}-TuRCs nucleate microtubules via a template-based mechanism in which the positions of {gamma}-tubulins in the {gamma}-TuSCs match the position of {gamma}-tubulin dimers in the microtubule lattice. Although {gamma}-TuSC proteins are highly conserved, other components of the {gamma}-TuRC can vary in different organisms, as can their relative importance. Here, we characterize two different simplified {gamma}-TuRCs from fission yeast Schizosaccharomyces pombe, using recombinant purified proteins and negative stain electron microscopy. We show that a nucleation-incompetent {gamma}-TuRC that contains only {gamma}-TuSC proteins plus the microprotein Mzt1 ({gamma}-TuSC:Mzt1) can form rings as efficiently as a large, nucleation-competent complex (MGM) that additionally contains the proteins Mto1 and Mto2. We find that the position of {gamma}-tubulins in {gamma}-TuSC:Mzt1 are less well defined than in MGM. Comparative modelling using our electron microscopy and crosslinking mass spectrometry data, together with structures of {gamma}-TuRCs from other organisms, suggests that Mto1 and Mto2 form a multimeric outer mantle surrounding the {gamma}-TuSC:Mzt1 {gamma}-TuRC. This mantle may stabilize positions of {gamma}-tubulins within MGM, explaining the microtubule-nucleating ability of MGM and highlighting the diversity of non-{gamma}-TuSC proteins in modulating {gamma}-TuRC structure and function.

biochemistry↗

Effects of Hypopigmentation Alleles and Ancestry on Skin Color in the Kalinago of Dominica

Our interest in the genetic basis of skin color variation between populations led us to seek a Native American population with African admixture but low frequency of European light skin alleles. Analysis of 458 genomes from individuals residing in the Kalinago territory of the Commonwealth of Dominica showed approximately 55% Native American, 32% African, and 12% European ancestry, the highest Native American ancestry among Caribbean populations to date. Skin pigmentation ranged from 20 to 80 melanin units, averaging 46. Three albino individuals were determined to be homozygous for a causative multi-nucleotide polymorphism OCA2NW273KV contained within a haplotype of African origin; its allele frequency was 0.03 and single allele effect size was -8 melanin units. Derived allele frequencies of SLC24A5A111T and SLC45A2L374F were 0.14 and 0.06, with single allele effect sizes of -6 and -4, respectively. Native American ancestry by itself reduced pigmentation by more than 20 melanin units (range 24 - 29). The responsible hypopigmenting genetic variants remain to be identified, since none of the published polymorphisms predicted in prior literature to affect skin color in Native Americans caused detectable hypopigmentation in the Kalinago.

genetics↗