RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair

Cellular DNA is under constant attack by a wide variety of agents, both endogenous and exogenous. To counteract DNA damage, human cells have a large collection of DNA repair factors. Among them, DNA polymerase lambda (Polλ) stands out for its versatility, as it participates in different DNA repair and damage tolerance pathways in which gap-filling DNA synthesis is required. In this work we show that human Polλ is conjugated with Small Ubiquitin-like MOdifier (SUMO) proteins both in vitro and in vivo, with Lys27 being the main target of this covalent modification. Polλ SUMOylation takes place in the nuclear pore complex and is mediated by the E3 ligase RanBP2. This post-translational modification promotes Polλ entry into the nucleus, which is required for its recruitment to DNA lesions and stimulated by DNA damage induction. Our work represents an advance in the knowledge of molecular pathways that regulate cellular localization of human Polλ, which are essential to be able to perform its functions during repair of nuclear DNA, and that might constitute an important point for the modulation of its activity in human cells

Regulation of human Polλ by ATM-mediated phosphorylation during Non-Homologous End Joining

DNA double strand breaks (DSBs) trigger a variety of cellular signaling processes, collectively termed the DNA-damage response (DDR), that are primarily regulated by protein kinase ataxia-telangiectasia mutated (ATM). Among DDR activated processes, the repair of DSBs by non-homologous end joining (NHEJ) is essential. The proper coordination of NHEJ factors is mainly achieved through phosphorylation by an ATM-related kinase, the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), although the molecular basis for this regulation has yet to be fully elucidated. In this study we identify the major NHEJ DNA polymerase, DNA polymerase lambda (Polλ), as a target for both ATM and DNA-PKcs in human cells. We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ. Molecular evidence suggests that Polλ phosphorylation might favor Polλ interaction with the DNA-PK complex at DSBs. Altogether, our work provides the first demonstration of how Polλ is regulated by phosphorylation to connect with the NHEJ core machinery during DSB repair in human cells.España MINECO y la Comisión Europea (European Regional Development Fund) to J.F.R. RYC-2011-08752, BFU2013-44343-P) and to F.C-L. (SAF2014-55532-R)

Técnicas de procesado de señal aplicadas al tratamiento de espectros Raman

Peer Reviewe

Morphology-based automated baseline removal for raman spectra of artistic pigments

The interpretation of a Raman spectrum is based on the identification of its characteristic molecular bands. However, the assignment of the vibrational modes is often compromised by the presence in the spectrum of an intense fluorescence background that covers the measured spectra. Several techniques have been employed to minimize the presence of this fluorescence in order to resolve and analyze Raman spectra. In this paper a new automated method for fluorescence subtraction is described, based on morphology operations. This method is compared with the most commonly used polynomial fitting methods. Results indicate that the proposed automated method is efficient in fluorescence subtraction and retains the line shapes and positions of the Raman bands in the spectra.Postprint (published version

Reduction of pulse distortion in travelling wave semiconductor optical amplifiers

The possibility of reducing the gain saturation during the pulse amplification process by means of the compensation of the carrier density variations is investigated. This should be useful in many optical systems and, especially, in high-speed communication systems.Peer ReviewedPostprint (published version

Myopic maculopathy: Current status and proposal for a new classification and grading system (ATN)

Myopia is a highly frequent ocular disorder worldwide and pathologic myopia is the 4th most common cause of irreversible blindness in developed countries. Pathologic myopia is especially common in East Asian countries. Ocular alterations associated with pathologic myopia, especially those involving the macular area—defined as myopic maculopathy—are the leading causes of vision loss in patients with pathologic myopia. High myopia is defined as the presence of a highly negative refractive error (>−6 to −8 diopters) in the context of eye elongation (26–26.5 mm). Although the terms high myopia and pathologic myopia are often used interchangeably, they do not refer to the same eye disease. The two key factors driving the development of pathologic myopia are: 1) elongation of the axial length and 2) posterior staphyloma. The presence of posterior staphyloma, which is the most common finding in patients with pathologic myopia, is the key differentiating factor between high and pathologic myopia. The occurrence of staphyloma will, in most cases, eventually lead to other conditions such as atrophic, traction, or neovascular maculopathy. Posterior staphyloma is for instance, responsible for the differences between a myopic macular hole (MH)—with and without retinal detachment—and idiopathic MH. Posterior staphyloma typically induces retinal layer splitting, leading to foveoschisis in myopic MH, an important differentiating factor between myopic and emmetropic MH. Myopic maculopathy is a highly complex disease and current classification systems do not fully account for the numerous changes that occur in the macula of these patients. Therefore, a more comprehensive classification system is needed, for several important reasons. First, to more precisely define the disease stage to improve follow-up by enabling clinicians to more accurately monitor changes over time, which is essential given the progressive nature of this condition. Second, unification of the currently-available classification systems would establish standardized classification criteria that could be used to compare the findings from international multicentric studies. Finally, a more comprehensive classification system could help to improve our understanding of the genetic origins of this disease, which is clearly relevant given the interchangeable—but erroneous—use of the terms high and pathologic myopia in genetic researc

Oestrid myiasis in European Mouflon from Spain

From February 1992 to March 1997, 245 European mouflon (Ovis orientalis musimon) from Sierras de Cazorla, Segura y Las Villas Natural Park (southern Spain) were surveyed for oestrid larvae in order to estimate prevalence and mean intensity of parasitism by Oestrus ovis. Over 46 percent of the animals surveyed were infected, with a mean intensity of 9.6 larvae/host parasitized. No significant differences in prevalence rates between host sexes were observed, but older mouflons were infected with more larvae than younger ones.Peer Reviewe

La espectroscopía raman aplicada a la identificación de materiales pictóricos

Peer ReviewedPostprint (published version