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The progression of a normal cell to senescence in vivo and in vitro is accompanied by a reduction in the length of the telomeres, the chromosome capping segments at the end of each linkage group. However, overexpression of the reverse transcriptase subunit (HTERT) of the ribonucleoprotein telomerase restores telomere length and delays cellular senescence. Although some data exist in the literature with respect to survival, no molecular data have shown that DNA repair in telomerase-immortalized cells is normal. Several telomerase-immortalized human skin fibroblast cell lines were constructed from a primary human fibroblast cell line. The primary line and the telomerase-immortalized cell lines were treated with either ultraviolet (UV) radiation or dimethylsulfate (DMS). UV radiation principally produces cyclobutane pyrimidine dimers that are repaired by nucleotide excision repair, whereas DMS introduces mainly N-methylpurines repaired by base excision repair. Here, we show that repair of both types of damage in the telomerase-immortalized human skin fibroblast cell lines is identical to repair observed in normal skin fibroblasts. Thus, telomerase expression and consequent immortalization of skin fibroblasts do not alter nucleotide or base excision repair in human cells.

Human 3-methyladenine-DNA glycosylase (MPG protein) is involved in the base excision repair (BER) pathway responsible mainly for the repair of small DNA base modifications. It initiates BER by recognizing DNA adducts and cleaving the glycosylic bond leaving an abasic site. Here, we explore several of the factors that could influence excision of adducts recognized by MPG, including sequence context, effect of APE1, and interaction with other proteins. To investigate sequence context, we used 13 different 25 bp oligodeoxyribonucleotides containing a unique hypoxanthine residue (Hx) and show that the steady-state specificity of Hx excision by MPG varied by 17-fold. If APE1 protein is used in the reaction for Hx removal by MPG, the steady-state kinetic parameters increase by between fivefold and 27-fold, depending on the oligodeoxyribonucleotide. Since MPG has a role in removing adducts such as 3-methyladenine that block DNA synthesis and there is a potential sequence for proliferating cell nuclear antigen (PCNA) interaction, we hypothesized that MPG protein could interact with PCNA, a protein involved in repair and replication. We demonstrate that PCNA associates with MPG using immunoprecipitation with either purified proteins or whole cell extracts. Moreover, PCNA binds to both APE1 and MPG at different sites, and loading PCNA onto a nicked, closed circular substrate with a unique Hx residue enhances MPG catalyzed excision. These data are consistent with an interaction that facilitates repair by MPG or APE1 by association with PCNA. Thus, PCNA could have a role in short-patch BER as well as in long-patch BER. Overall, the data reported here show how multiple factors contribute to the activity of MPG in cells.

Seismic lines and sediment cores collected along the shelf between Albenga and Loano (Liguria, NW Italy) allowed an unprecedented reconstruction of the characters and distribution of late Quaternary transgressive littoral deposits. Multiple seismic lines datasets and stratigraphic logs were managed within a single, GIS-based software. This approach allowed the merging, analysis, and interpretation of multimethodological datasets, greatly increasing the understanding of the study area. On seismic reflection lines, the identification of high-amplitude acoustic facies (i.e. coarse-grained deposits), coupled with the analyses of the identified paleo-morphologies, allowed the mapping of (at least) five paleo shorelines along the continental shelf at 30–40 40–60, 60–80, 80–90 and 90–100 m below sea level. Their retrogradiational geometry and terraced distribution likely indicate episodic, stepwise retreats of Late Quaternary coastal system (last 18–11 Ky), compatible with phases of fast sea level rise interspersed by long periods of sea level stillstand. [ABSTRACT FROM AUTHOR]

Recent models propose that the exhumation of high-pressure rocks occurs by means of return flow inside a low-viscosity channel of serpentinite situated between the plates. To test this hypothesis, we investigated a serpentinite melange in the Western Alps, which contains exotic mafic and metasedimentary tectonic blocks, recording heterogeneous metamorphic evolutions and variable high-pressure ages. The peak metamorphic conditions range from eclogite- to garnet-blueschist-facies. The structural evidence and the pressure-temperature paths of the different blocks suggest coupling between blocks and matrix, at least in the blueschist facies. [sup.39]Ar-[sup.40]Ar dating indicates eclogite-facies peak at ca. 43 Ma and blueschist-facies peak at ca. 43 and 40 Ma in different blocks, respectively. These data point to diachronous metamorphic paths resulting from independent tectonic evolutions of the different slices. We therefore propose that this melange formed during exhumation of subducted rocks equilibrated at different depths inside a subduction channel. This mechanism can be extended to other serpentinite melanges in the Alps and other orogens (e.g., the Cyclades, the Coast Ranges of California) for which a growing heterogeneity in the timing of metamorphic equilibration and of pressure-temperature paths can be expected with further investigations. Keywords: subduction channel; tectonic melange; Western Alps; high-pressure, [sup.39]Ar-[sup.40]Ar geochronology