Heath, J. | bioRxiv Science

bioRxiv2018

FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice.

DNA double-strand breaks (DSBs) can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). DNA repair pathway choice is governed by the opposing activities of 53BP1, in complex with its effectors RIF1 and REV7, and BRCA1. However, it remains unknown how the 53BP1/RIF1/REV7 complex stimulates NHEJ and restricts HR to the S/G2 phases of the cell cycle. Using a mass spectrometry (MS)-based approach, we identify 11 high-confidence REV7 interactors and elucidate the role of a previously undescribed factor, FAM35A/SHDL2, as a novel effector of REV7 in the NHEJ pathway. FAM35A depletion impairs NHEJ-mediated DNA repair and compromises antibody diversification by class switch recombination (CSR) in B-cells. FAM35A accumulates at DSBs in a 53BP1-, RIF1- and REV7-dependent manner and antagonizes HR by limiting DNA end resection. In fact, FAM35A is part of a larger complex composed of REV7 and another previously uncharacterized protein, C20orf196/SHDL1, which promotes NHEJ and limits HR. Together, these results establish FAM35A as a novel effector of REV7 in controlling the decision-making process during DSB repair.

cancer biology↗

bioRxiv2017

Rare earth elements (REE) in freshwater, marine, and terrestrial ecosystems in the eastern Canadian Arctic

Few ecotoxicological studies exist for rare earth elements (REEs), particularly field-based studies on their bioaccumulation and food web dynamics. REE mining has led to significant environment impacts in several countries (China, Brazil, U.S.), yet little is known about the fate and transport of these contaminants of emerging concern. To understand how REEs behave in pristine northern food webs, we measured REE concentrations and carbon and nitrogen stable isotope ratios ({partial}15N, {partial}13C) in biota from marine, freshwater, and terrestrial ecosystems of the eastern Canadian Arctic (N=339). Northern ecosystems are potentially vulnerable to REE enrichment from prospective mining projects at high latitudes. Wildlife harvesting and tissue sampling was partly conducted by local hunters through a community-based monitoring project. Results show that REE generally follow a coherent bioaccumulation pattern for sample tissues, with some anomalies for redox-sensitive elements (Ce, Eu). Highest REE concentrations were found at low trophic levels, especially in vegetation and aquatic invertebrates. Terrestrial herbivores, ringed seal, and fish had low REE levels in muscle tissue (<0.1 nmolg-1), yet accumulation was an order of magnitude higher in all liver tissues. Age- and length-dependent REE accumulation also suggest that REE uptake is faster than elimination for some species. Overall, REE bioaccumulation patterns appear to be species- and tissue-species, with limited potential for biomagnification. This study provides novel ecotoxicological data on the behaviour of REE in ecosystems and will be useful for environmental impact assessment of REE enrichment in northern regions.

ecology↗