Excessive reactive oxygen species induce transcription-dependent replication stress.

Elevated levels of reactive oxygen species (ROS) reduce replication fork velocity by causing dissociation of the TIMELESS-TIPIN complex from the replisome. Here, we show that ROS generated by exposure of human cells to the ribonucleotide reductase inhibitor hydroxyurea (HU) promote replication fork reversal in a manner dependent on active transcription and formation of co-transcriptional RNA:DNA hybrids (R-loops). The frequency of R-loop-dependent fork stalling events is also increased after TIMELESS depletion or a partial inhibition of replicative DNA polymerases by aphidicolin, suggesting that this phenomenon is due to a global replication slowdown. In contrast, replication arrest caused by HU-induced depletion of deoxynucleotides does not induce fork reversal but, if allowed to persist, leads to extensive R-loop-independent DNA breakage during S-phase. Our work reveals a link between oxidative stress and transcription-replication interference that causes genomic alterations recurrently found in human cancer. [Abstract copyright: © 2023. The Author(s).

Hubble Space Telescope Observations of cD Galaxies and their Globular Cluster Systems

We have used WFPC2 on the Hubble Space Telescope to obtain F450W and F814W images of four cD galaxies (NGC 541 in Abell 194, NGC 2832 in Abell 779, NGC 4839 in Abell 1656 and NGC 7768 in Abell 2666) in the range 5400 < cz < 8100 km s^{-1}. For NGC 541, the HST data are supplemented by ground-based B and I images obtained with the FORS1 on the VLT. We present surface brightness and color profiles for each of the four galaxies, confirming their classification as cD galaxies. Isophotal analyses reveal the presence of subarcsecond-scale dust disks in the nuclei of NGC 541 and NGC 7768. Despite the extreme nature of these galaxies in terms of spatial extent and luminosity, our analysis of their globular cluster systems reveals no anomalies in terms of specific frequencies, metallicity gradients, average metallicities, or the metallicity offset between the globulars and the host galaxy. We show that the latter offset appears roughly constant at \Delta [Fe/H] ~ 0.8 dex for early-type galaxies spanning a luminosity range of roughly four orders of magnitude. We combine the globular cluster metallicity distributions with an empirical technique described in a series of earlier papers to investigate the form of the protogalactic mass spectrum in these cD galaxies. We find that the observed GC metallicity distributions are consistent with those expected if cD galaxies form through the cannibalism of numerous galaxies and protogalactic fragments which formed their stars and globular clusters before capture and disruption. However, the properties of their GC systems suggest that dynamical friction is not the primary mechanism by which these galaxies are assembled. We argue that cDs instead form rapidly, via hierarchical merging, prior to cluster virialization.Comment: 36 pages, 20 postscript figures, uses emulateapj. Accepted for publication in the Astronomical Journa

Editorial Special Issue On Photonic Crystal-based Sensors

[No abstract available]1071167116