Catálogo de publicaciones - revistas

<jats:title>Abstract</jats:title><jats:p>Humans evolved in a patchwork of semi-connected populations across Africa<jats:sup>1,2</jats:sup>; understanding when and how these groups connected is critical to interpreting our present-day biological and cultural diversity. Genetic analyses reveal that eastern and southern African lineages diverged sometime in the Pleistocene epoch, approximately 350–70 thousand years ago (ka)<jats:sup>3,4</jats:sup>; however, little is known about the exact timing of these interactions, the cultural context of these exchanges or the mechanisms that drove their separation. Here we compare ostrich eggshell bead variations between eastern and southern Africa to explore population dynamics over the past 50,000 years. We found that ostrich eggshell bead technology probably originated in eastern Africa and spread southward approximately 50–33 ka via a regional network. This connection breaks down approximately 33 ka, with populations remaining isolated until herders entered southern Africa after 2 ka. The timing of this disconnection broadly corresponds with the southward shift of the Intertropical Convergence Zone, which caused periodic flooding of the Zambezi River catchment (an area that connects eastern and southern Africa). This suggests that climate exerted some influence in shaping human social contact. Our study implies a later regional divergence than predicted by genetic analyses, identifies an approximately 3,000-kilometre stylistic connection and offers important new insights into the social dimension of ancient interactions.</jats:p>

<jats:title>Abstract</jats:title><jats:p>Cancer is a ubiquitous disease of metazoans, predicted to disproportionately affect larger, long-lived organisms owing to their greater number of cell divisions, and thus increased probability of somatic mutations<jats:sup>1,2</jats:sup>. While elevated cancer risk with larger body size and/or longevity has been documented within species<jats:sup>3–5</jats:sup>, Peto’s paradox indicates the apparent lack of such an association among taxa<jats:sup>6</jats:sup>. Yet, unequivocal empirical evidence for Peto’s paradox is lacking, stemming from the difficulty of estimating cancer risk in non-model species. Here we build and analyse a database on cancer-related mortality using data on adult zoo mammals (110,148 individuals, 191 species) and map age-controlled cancer mortality to the mammalian tree of life. We demonstrate the universality and high frequency of oncogenic phenomena in mammals and reveal substantial differences in cancer mortality across major mammalian orders. We show that the phylogenetic distribution of cancer mortality is associated with diet, with carnivorous mammals (especially mammal-consuming ones) facing the highest cancer-related mortality. Moreover, we provide unequivocal evidence for the body size and longevity components of Peto’s paradox by showing that cancer mortality risk is largely independent of both body mass and adult life expectancy across species. These results highlight the key role of life-history evolution in shaping cancer resistance and provide major advancements in the quest for natural anticancer defences.</jats:p>

<jats:title>Abstract</jats:title><jats:p>DNA double-stranded breaks (DSBs) are deleterious lesions, and their incorrect repair can drive cancer development<jats:sup>1</jats:sup>. HELQ is a superfamily 2 helicase with 3′ to 5′ polarity, and its disruption in mice confers germ cells loss, infertility and increased predisposition to ovarian and pituitary tumours<jats:sup>2–4</jats:sup>. At the cellular level, defects in HELQ result in hypersensitivity to cisplatin and mitomycin C, and persistence of RAD51 foci after DNA damage<jats:sup>3,5</jats:sup>. Notably, HELQ binds to RPA and the RAD51-paralogue BCDX2 complex, but the relevance of these interactions and how HELQ functions in DSB repair remains unclear<jats:sup>3,5,6</jats:sup>. Here we show that HELQ helicase activity and a previously unappreciated DNA strand annealing function are differentially regulated by RPA and RAD51. Using biochemistry analyses and single-molecule imaging, we establish that RAD51 forms a complex with and strongly stimulates HELQ as it translocates during DNA unwinding. By contrast, RPA inhibits DNA unwinding by HELQ but strongly stimulates DNA strand annealing. Mechanistically, we show that HELQ possesses an intrinsic ability to capture RPA-bound DNA strands and then displace RPA to facilitate annealing of complementary sequences. Finally, we show that HELQ deficiency in cells compromises single-strand annealing and microhomology-mediated end-joining pathways and leads to bias towards long-tract gene conversion tracts during homologous recombination. Thus, our results implicate HELQ in multiple arms of DSB repair through co-factor-dependent modulation of intrinsic translocase and DNA strand annealing activities.</jats:p>