BRCA1-BARD1: the importance of being in shape

The breast cancer type-1 susceptibility protein (BRCA1) contributes to genome integrity through homologous recombinational DNA repair and by protecting stalled replication forks from nucleolytic degradation. We recently discovered that fork protection requires a conformational change of BRCA1 unimportant to homologous recombination repair, indicating separate roles for BRCA1 in these pathways

Human BRCA1-BARD1 ubiquitin ligase activity counters chromatin barriers to DNA resection

The opposing activities of 53BP1 and BRCA1 influence pathway choice of DNA double-strand break repair. How BRCA1 counters the inhibitory effect of 53BP1 on DNA resection and homologous recombination is unknown. Here we identify the site of BRCA1-BARD1 required for priming ubiquitin transfer from E2~ubiquitin. We demonstrate that BRCA1-BARD1’s ubiquitin ligase activity is required for repositioning 53BP1 on damaged chromatin. We confirm H2A ubiquitylation by BRCA1-BARD1 and show that an H2A-ubiquitin fusion protein promotes DNA resection and repair in BARD1 deficient cells. We show BRCA1-BARD1 function in homologous recombination requires the chromatin remodeler SMARCAD1. SMARCAD1 binding to H2A-ubiquitin, optimal localization to sites of damage and activity in DNA repair requires its ubiquitin-binding CUE domains. SMARCAD1 is required for 53BP1 repositioning and the need for SMARCAD1 in Olaparib or camptothecin resistance is alleviated by 53BP1 loss. Thus BRCA1- BARD1 ligase activity and subsequent SMARCAD1-dependent chromatin remodeling are critical regulators of DNA repair

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expert´s group based and informed on evidence

La Asociación Colombiana de Infectología (ACIN) y el Instituto de Evaluación de Nuevas Tecnologías de la Salud (IETS) conformó un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atención, diagnóstico y manejo de casos de Covid 19. Estas guías son dirigidas al personal de salud y buscar dar recomendaciones en los ámbitos de la atención en salud de los casos de Covid-19, en el contexto nacional de Colombia

Characterisation of a novel BRCA1 regulation required for the protection of stalled DNA replication forks

Lesions in DNA can lead to accumulation of mutations that may cause cancer progression and disease. DNA repair is essential to overcome these lesions maintaining genomic integrity and preserving the genetic information, following DNA damage a wide variety of post-translational modifications (PTM) take place and phosphorylation is an essential one. A key DNA repair factor is BRCA1, a tumour suppressor gene that encodes a protein that can form 3 different complexes implicated in several mechanisms of DNA repair, interestingly BRCA1 mutations can lead to an increased risk of having breast and ovarian cancer by the age of 70. An important binding partner of BRCA1 is PALB2 a cancer predisposition gene that is essential for accurate HR repair, however it is yet not well understood whether the BRCA1-PALB2 interaction is involved in other DNA repair mechanisms. An important role of BRCA1 is to promote replication fork stability by protecting nascent DNA at stalled replication forks from degradation, and this function is essential to preserve genomic integrity but it remains unclear how BRCA1 regulates replication fork stability and fork protection. In this thesis we suggest that the ability of BRCA1 to protect nascent DNA is regulated in an unexpected fashion through CDK phosphorylation at Serine 114 and PIN1-mediated conformational change. Our data also reveals dual roles of PALB2 and BRCA1 at stalled replication forks, as restart and protection are separate, and interestingly unclassified patient variants within the CDK-PIN1 regulated region of BRCA1 exhibit deleterious fork protection. Altogether findings in this thesis suggest a previously unrecognised regulation pathway where CDK1, 2-BRCA1-PIN1-PALB2 cooperate together to govern fork stability

Altered immune parameters correlate with infection-related hospitalizations in children with Down syndrome

Q4Q2Artículo original594-599In addition to previously studied immunological variables, the relative expression of IFNGR2, IFNAR1,CD18, and CD275 (all encoded in chromosome 21) on circulating leucocytes and multifunctional T cells(evaluated by an intracellular cytokine/proliferation assay) were compared between children with Downsyndrome (DS) and healthy controls (HC). As previously reported, numbers of lymphocytes, CD4+T cells,Treg cells, B cells, and levels of serum IgM were decreased, and levels of IgG and IgA were increased inchildren with DS. Moreover, the relative expression of CD18 on T and B cells (previously and not previ-ously reported, respectively) were elevated in DS children (p60.01). Age and numbers of B and Treg cellsmoderately correlated with retrospectively identified infection related hospitalizations (rho: 0.300–0.460, p60.003). Age and the numbers of Treg cells also correlated with prospectively identified infec-tion related hospitalizations. Future studies are necessary to clarify the role of these parameters in theimmunity of DS patient