Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability

Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA polymerase II, causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions. However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR-Cas9 screen, we identified the elongation factor ELOF1 as an important factor in the transcription stress response following DNA damage. We show that ELOF1 has an evolutionarily conserved role in transcription-coupled nucleotide excision repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair transcription-blocking lesions and resume transcription. Additionally, ELOF1 modulates transcription to protect cells against transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage via two distinct mechanisms

Insights into the Complex Associations Between MHC Class II DRB Polymorphism and Multiple Gastrointestinal Parasite Infestations in the Striped Mouse

Differences in host susceptibility to different parasite types are largely based on the degree of matching between immune genes and parasite antigens. Specifically the variable genes of the major histocompatibility complex (MHC) play a major role in the defence of parasites. However, underlying genetic mechanisms in wild populations are still not well understood because there is a lack of studies which deal with multiple parasite infections and their competition within. To gain insights into these complex associations, we implemented the full record of gastrointestinal nematodes from 439 genotyped individuals of the striped mouse, Rhabdomys pumilio. We used two different multivariate approaches to test for associations between MHC class II DRB genotype and multiple nematodes with regard to the main pathogen-driven selection hypotheses maintaining MHC diversity and parasite species-specific co-evolutionary effects. The former includes investigations of a ‘heterozygote advantage’, or its specific form a ‘divergent-allele advantage’ caused by highly dissimilar alleles as well as possible effects of specific MHC-alleles selected by a ‘rare allele advantage’ ( = negative ‘frequency-dependent selection’). A combination of generalized linear mixed models (GLMMs) and co-inertia (COIA) analyses made it possible to consider multiple parasite species despite the risk of type I errors on the population and on the individual level. We could not find any evidence for a ‘heterozygote’ advantage but support for ‘divergent-allele’ advantage and infection intensity. In addition, both approaches demonstrated high concordance of positive as well as negative associations between specific MHC alleles and certain parasite species. Furthermore, certain MHC alleles were associated with more than one parasite species, suggesting a many-to-many gene-parasite co-evolution. The most frequent allele Rhpu-DRB*38 revealed a pleiotropic effect, involving three nematode species. Our study demonstrates the co-existence of specialist and generalist MHC alleles in terms of parasite detection which may be an important feature in the maintenance of MHC polymorphism

Genetic connectivity of the ecosystem engineer Perumytilus purpuratus north to the 32ºS southeast Pacific ecological discontinuity

Connectivity in benthic marine animals with complex life cycles occurs primarily during the pelagic lar-val stage and depends deterministically on oceanographic dynamics. The scale of such larval dispersal is highly uncertain due the difficulty of direct measurement and poor knowledge of larval dynamics and ocean flow variability. This study characterizes the pattern of genetic connectivity in the ecosystem engineer Perumytilus purpuratus between latitudes 23°S and 33°S, which includes the ecological discontinuity reported for many taxa north to 32°S at the southeast Pacific. The genetic discontinuity observed in P. purpuratus around 26°S is described herein while that detected at 28°S is in line with the ecological discontinuity (in coverage, recruitment and density) previously reported for this mussel between 28°S and 32°S. Both discontinui-ties delimitate two major gene pools upon Bayesian infer-ences on geographical variation of five microsatellite loci. Interestingly, marker Pepu 1 was responsible for most vari-ation between pools and was potentially under selection. In fact, inferences excluding Pepu 1 produced a single gene pool ( k = 1) in central-northern Chile. The IBD connec-tivity pattern observed among P. purpuratus beds distrib-uted in the interval 23°S–33°S is congruent with processes driven by larval dynamics, and the dominant equatorward Humboldt Current along a coast largely unaffected by ice during the last Pleistocene glaciation. However, the selec-tive scenario unveiled by microsatellite Pepu 1 inside the 25°S–28°S ecological discontinuity is consistent with selective processes associated with specific mesoscale properties operating in this area. This study highlights the usefulness of integrating different oceanographic scales, ecological data and population genetics to better under-stand connectivity of benthic marine species.Versión del editor2,011

In search of decoy/guardee to R genes: Deciphering the role of sugars in defense against Fusarium wilt in chickpea

Plant responses are coordinately controlled by both external and internal signals. Apt perception of pathogen attack and its appropriate conversion to internal signals ultimately determine the outcome of innate immunity. The present review predicts the involvement of unconventional ‘guard/decoy model’ in chickpea-Fusarium encounter. Rapid alkalinization factor is predicted to act as initial ‘Gatekeeper decoy’ counteracting fungal entry. Phospholipases and cystatins probably function as ‘Guardees’ being shielded by R gene(s). Serine Threonine Kinases decodes external pathogenic signals to in planta defense alarms. 14.3.3 provides clues to the wilt mechanism. The versatile sugars serve as signal generators and transmitters maintaining intra and inter cellular connectivity during stress