Human base excision repair complex is physically associated to DNA replication and cell cycle regulatory proteins

It has been hypothesized that a replication associated repair pathway operates on base damage and single strand breaks (SSB) at replication forks. In this study, we present the isolation from the nuclei of human cycling cells of a multiprotein complex containing most of the essential components of base excision repair (BER)/SSBR, including APE1, UNG2, XRCC1 and POLβ, DNA PK, replicative POLα, δ and ɛ, DNA ligase 1 and cell cycle regulatory protein cyclin A. Co-immunoprecipitation revealed that in this complex DNA repair proteins are physically associated to cyclin A and to DNA replication proteins including MCM7. This complex is endowed with DNA polymerase and protein kinase activity and is able to perform BER of uracil and AP sites. This finding suggests that a preassembled DNA repair machinery is constitutively active in cycling cells and is ready to be recruited at base damage and breaks occurring at replication forks

The type of DNA glycosylase determines the base excision repair pathway in mammalian cells.

The base excision repair (BER) of modified nucleotides is initiated by damage-specific DNA glycosylases. The repair of the resulting apurinic/apyrimidinic site involves the replacement of either a single nucleotide (short patch BER) or of several nucleotides (long patch BER). The mechanism that controls the selection of either BER pathway is unknown. We tested the hypothesis that the type of base damage present on DNA, by determining the specific DNA glycosylase in charge of its excision, drives the repair of the resulting abasic site intermediate to either BER branch. In mammalian cells hypoxanthine (HX) and 1,N6-ethenoadenine (epsilonA) are both substrates for the monofunctional 3-methyladenine DNA glycosylase, the ANPG protein, whereas 7,8-dihydro-8-oxoguanine (8-oxoG) is removed by the bifunctional DNA glycosylase/beta-lyase 8-oxoG-DNA gly- cosylase (OGG1). Circular plasmid molecules containing a single HX, epsilonA, or 8-oxoG were constructed. In vitro repair assays with HeLa cell extracts revealed that HX and epsilonA are repaired via both short and long patch BER, whereas 8-oxoG is repaired mainly via the short patch pathway. The preferential repair of 8-oxoG by short patch BER was confirmed by the low efficiency of repair of this lesion by DNA polymerase beta-deficient mouse cells as compared with their wild-type counterpart. These data fit into a model where the intrinsic properties of the DNA glycosylase that recognizes the lesion selects the branch of BER that will restore the intact DNA template

Are there more galaxies than we see around high-zz quasars?

Whether or not $z \gtrsim 6$ quasars lie in the most massive dark-matter halos of the Universe is still a subject of dispute. While most theoretical studies support this scenario, current observations yield discordant results when they probe the halo mass through the detection rate of quasar companion galaxies. Feedback processes from supermassive black holes and dust obscuration have been blamed for this discrepancy, but the impact of these effects is complex and far from being clearly understood. This paper aims to improve the interpretation of current far-infrared observations by taking into account the cosmological volume probed by the Atacama Large Millimeter/submillimeter Array Telescope and to explain the observational discrepancies. We statistically investigate the detection rate of quasar companions in current observations and verify if they match the expected distribution from various theoretical models, once convolved with the ALMA field-of-view, through the use of Monte Carlo simulations. We demonstrate that the telescope geometrical bias is fundamental and can alone explain the scatter in the number of detected satellite galaxies in different observations. We conclude that the resulting companion densities depend on the chosen galaxy distributions. According to our fiducial models, current data favour a density scenario where quasars lie in dark-matter halos of viral mass $M_{\rm vir} \gtrsim 10^{12}~{\rm M_{\odot}}$, in agreement with most theoretical studies. According to our analysis, each quasar has about 2 companion galaxies, with a [CII] luminosity $L_{\rm [CII]} \gtrsim 10^8~{\rm L}_{\odot}$, within a distance of about 1~Mpc from the quasar.Comment: 7 pages, 5 figures; accepted for publications in A&

Misexpression of a chloroplast aspartyl protease leads to severe growth defects and alters carbohydrate metabolism in Arabidopsis

The crucial role of carbohydrate in plant growth and morphogenesis is widely recognized. In this study, we describe the characterization of nana, a dwarf Arabidopsis (Arabidopsis thaliana) mutant impaired in carbohydrate metabolism. We show that the nana dwarf phenotype was accompanied by altered leaf morphology and a delayed flowering time. Our genetic and molecular data indicate that the mutation in nana is due to a transfer DNA insertion in the promoter region of a gene encoding a chloroplast-located aspartyl protease that alters its pattern of expression. Overexpression of the gene (oxNANA) phenocopies the mutation. Both nana and oxNANA display alterations in carbohydrate content, and the extent of these changes varies depending on growth light intensity. In particular, in low light, soluble sugar levels are lower and do not show the daily fluctuations observed in wild-type plants. Moreover, nana and oxNANA are defective in the expression of some genes implicated in sugar metabolism and photosynthetic light harvesting. Interestingly, some chloroplast-encoded genes as well as genes whose products seem to be involved in retrograde signaling appear to be down-regulated. These findings suggest that the NANA aspartic protease has an important regulatory function in chloroplasts that not only influences photosynthetic carbon metabolism but also plastid and nuclear gene expression

Bubbles and outflows: the novel JWST/NIRSpec view of the z=1.59 obscured quasar XID2028

Quasar feedback in the form of powerful outflows is invoked as a key mechanism to quench star formation in galaxies, although direct observational evidence is still scarce and debated. Here we present Early Release Science JWST NIRSpec IFU observations of the z=1.59 prototypical obscured quasar XID2028: this target represents a unique test case to study QSO feedback at the peak epoch of AGN-galaxy co-evolution thanks to its existing extensive multi-wavelength coverage and massive and extended outflow detected both in the ionised and molecular components. With the unprecedented sensitivity and spatial resolution of JWST, the NIRSpec dataset reveals a wealth of structures in the ionised gas kinematics and morphology previously hidden in the seeing-limited ground-based data. In particular, we find evidence of interaction between the interstellar medium of the galaxy and the QSO-driven outflow and radio jet, which is producing an expanding bubble from which the fast and extended wind detected in previous observations is emerging. The new observations confirm the complex interplay between the AGN jet/wind and the ISM of the host galaxy, highlighting the role of low luminosity radio jets in AGN feedback, and showcase the new window opened by NIRSpec on the detailed study of feedback at high redshift.Comment: 12 pages, 11 figures, submitted to A&A. Comments welcom

A fast-rotator post-starburst galaxy quenched by supermassive black-hole feedback at z=3

There is compelling evidence that the most massive galaxies in the Universe stopped forming stars due to the time-integrated feedback from their central super-massive black holes (SMBHs). However, the exact quenching mechanism is not yet understood, because local massive galaxies were quenched billions of years ago. We present JWST/NIRSpec integral-field spectroscopy observations of GS-10578, a massive, quiescent galaxy at redshift z=3.064. From the spectrum we infer that the galaxy has a stellar mass of $M_*=1.6\pm0.2 \times 10^{11}$ MSun and a dynamical mass $M_{\rm dyn}=2.0\pm0.5 \times 10^{11}$ MSun. Half of its stellar mass formed at z=3.7-4.6, and the system is now quiescent, with the current star-formation rate SFR<9 MSun/yr. We detect ionised- and neutral-gas outflows traced by [OIII] emission and NaI absorption. Outflow velocities reach $v_{\rm out}\approx$1,000 km/s, comparable to the galaxy escape velocity and too high to be explained by star formation alone. GS-10578 hosts an Active Galactic Nucleus (AGN), evidence that these outflows are due to SMBH feedback. The outflow rates are 0.14-2.9 and 30-300 MSun/yr for the ionised and neutral phases, respectively. The neutral outflow rate is ten times higher than the SFR, hence this is direct evidence for ejective SMBH feedback, with mass-loading capable of interrupting star formation by rapidly removing its fuel. Stellar kinematics show ordered rotation, with spin parameter $\lambda_{Re}=0.62\pm0.07$, meaning GS-10578 is rotation supported. This study shows direct evidence for ejective AGN feedback in a massive, recently quenched galaxy, thus clarifying how SMBHs quench their hosts. Quenching can occur without destroying the stellar disc.Comment: 40 pages, 9 figures, submitted to Nat. Ast., comments welcome

JADES: Probing interstellar medium conditions at z∼5.5−9.5z\sim5.5-9.5 with ultra-deep JWST/NIRSpec spectroscopy

We present emission line ratios from a sample of 26 Lyman break galaxies from $z\sim5.5-9.5$ with $-17.0<M_{1500}<-20.4$, measured from ultra-deep JWST/NIRSpec MSA spectroscopy from JADES. We use 28 hour deep PRISM/CLEAR and 7 hour deep G395M/F290LP observations to measure, or place strong constraints on, ratios of widely studied rest-frame optical emission lines including H$\alpha$, H$\beta$, [OII] $\lambda\lambda$3726,3729, [NeIII] $\lambda$3869, [OIII] $\lambda$4959, [OIII] $\lambda$5007, [OI] $\lambda$6300, [NII] $\lambda$6583, and [SII] $\lambda\lambda$6716,6731 in individual $z>5.5$ spectra. We find that the emission line ratios exhibited by these $z\sim5.5-9.5$ galaxies occupy clearly distinct regions of line-ratio space compared to typical z~0-3 galaxies, instead being more consistent with extreme populations of lower-redshift galaxies. This is best illustrated by the [OIII]/[OII] ratio, tracing interstellar medium (ISM) ionisation, in which we observe more than half of our sample to have [OIII]/[OII]>10. Our high signal-to-noise spectra reveal more than an order of magnitude of scatter in line ratios such as [OII]/H$\beta$ and [OIII]/[OII], indicating significant diversity in the ISM conditions within the sample. We find no convincing detections of [NII] in our sample, either in individual galaxies, or a stack of all G395M/F290LP spectra. The emission line ratios observed in our sample are generally consistent with galaxies with extremely high ionisation parameters (log $U\sim-1.5$), and a range of metallicities spanning from $\sim0.1\times Z_\odot$ to higher than $\sim0.3\times Z_\odot$, suggesting we are probing low-metallicity systems undergoing periods of rapid star-formation, driving strong radiation fields. These results highlight the value of deep observations in constraining the properties of individual galaxies, and hence probing diversity within galaxy population.Comment: 20 pages, 9 figures, submitted to Astronomy & Astrophysics, updated values in table

The JADES Origins Field: A New JWST Deep Field in the JADES Second NIRCam Data Release

We summarize the properties and initial data release of the JADES Origins Field (JOF), which will soon be the deepest imaging field yet observed with the James Webb Space Telescope (JWST). This field falls within the GOODS-S region about 8' south-west of the Hubble Ultra Deep Field (HUDF), where it was formed initially in Cycle 1 as a parallel field of HUDF spectroscopic observations within the JWST Advanced Deep Extragalactic Survey (JADES). This imaging will be greatly extended in Cycle 2 program 3215, which will observe the JOF for 5 days in six medium-band filters, seeking robust candidates for z>15 galaxies. This program will also include ultra-deep parallel NIRSpec spectroscopy (up to 104 hours on-source, summing over the dispersion modes) on the HUDF. Cycle 3 observations from program 4540 will add 20 hours of NIRCam slitless spectroscopy to the JOF. With these three campaigns, the JOF will be observed for 380 open-shutter hours with NIRCam using 15 imaging filters and 2 grism bandpasses. Further, parts of the JOF have deep 43 hr MIRI observations in F770W. Taken together, the JOF will soon be one of the most compelling deep fields available with JWST and a powerful window into the early Universe. This paper presents the second data release from JADES, featuring the imaging and catalogs from the year 1 JOF observations.Comment: Submitted to ApJ Supplement. Images and catalogs are available at https://archive.stsci.edu/hlsp/jades . A FITSmap portal to view the images is at https://jades.idies.jhu.ed

JADES NIRSpec Spectroscopy of GN-z11: Lyman-α\alpha emission and possible enhanced nitrogen abundance in a z=10.60z=10.60 luminous galaxy

We present JADES JWST/NIRSpec spectroscopy of GN-z11, the most luminous candidate $z>10$ Lyman break galaxy in the GOODS-North field with $M_{UV}=-21.5$. We derive a redshift of $z=10.603$ (lower than previous determinations) based on multiple emission lines in our low and medium resolution spectra over $0.8-5.3\,\mu$m. We significantly detect the continuum and measure a blue rest-UV spectral slope of $\beta=-2.4$. Remarkably, we see spatially-extended Lyman-$\alpha$ in emission (despite the highly-neutral IGM expected at this early epoch), offset 555 km/s redward of the systemic redshift. From our measurements of collisionally-excited lines of both low- and high-ionization (including [O II] $\lambda3727$, [Ne III] $\lambda 3869$ and C III] $\lambda1909$) we infer a high ionization parameter ($\log U\sim -2$). We detect the rarely-seen N IV] $\lambda1486$ and N III]$\lambda1748$ lines in both our low and medium resolution spectra, with other high ionization lines seen in low resolution spectrum such as He II (blended with O III]) and C IV (with a possible P-Cygni profile). Based on the observed rest-UV line ratios, we cannot conclusively rule out photoionization from AGN. The high C III]/He II ratios, however, suggest a likely star-formation explanation. If the observed emission lines are powered by star formation, then the strong N III] $\lambda1748$ observed may imply an unusually high $N/O$ abundance. Balmer emission lines (H$\gamma$, H$\delta$) are also detected, and if powered by star formation rather than an AGN we infer a star formation rate of $\sim 20-30 M_{\odot}\,\rm yr^{-1}$ (depending on the IMF) and low dust attenuation. Our NIRSpec spectroscopy confirms that GN-z11 is a remarkable galaxy with extreme properties seen 430 Myr after the Big Bang.Comment: Submitted to Astronomy & Astrophysics, 14 pages, 9 figure