Chromatin modifiers alter recombination between divergent DNA sequences

Chakraborty, U.; Mackenroth, B.; Alani, E. E.

doi:10.1101/519397

Home/Archive/bioRxiv

bioRxiv · 10.1101/519397

Chromatin modifiers alter recombination between divergent DNA sequences

Chakraborty, U.·Mackenroth, B.·Alani, E. E.

View original source ↗Export metadata ↓

Abstract

Recombination between divergent DNA sequences is actively prevented by heteroduplex rejection mechanisms. In bakers yeast such anti-recombination mechanisms can be initiated by the recognition of DNA mismatches in heteroduplex DNA by MSH proteins, followed by recruitment of the Sgs1-Top3-Rmi1 helicase-topoisomerase complex to unwind the recombination intermediate. We previously showed that the repair/rejection decision during single-strand annealing recombination is temporally regulated by MSH protein levels and by factors that excise non-homologous single-stranded tails. These observations, coupled with recent studies indicating that mismatch repair factors interact with components of the histone chaperone machinery, encouraged us to explore roles for epigenetic factors and chromatin conformation in regulating the decision to reject vs. repair recombination between divergent DNA substrates. This work involved the use of an inverted repeat recombination assay thought to measure sister chromatid repair during DNA replication. Our observations are consistent with the histone chaperones CAF-1 and Rtt106 and the histone deacetylase Sir2 acting to suppress heteroduplex rejection and the Rpd3, Hst3 and Hst4 deacetylases acting to promote heteroduplex rejection. These observations and double mutant analysis have led to a model in which nucleosomes located at DNA lesions stabilize recombination intermediates and compete with mismatch repair factors that mediate heteroduplex rejection.\n\nSummaryRecombination between divergent DNA sequences is actively prevented by heteroduplex rejection mechanisms. In this study we explored roles for epigenetic factors and chromatin conformation in regulating the decision to reject vs. repair recombination between divergent DNA substrates. Our observations are consistent with the histone chaperones CAF-1 and Rtt106 and the histone deacetylase Sir2 acting to suppress heteroduplex rejection and the Rpd3, Hst3 and Hst4 deacetylases acting to promote heteroduplex rejection. These observations have led to a model in which nucleosomes located at DNA lesions stabilize recombination intermediates and compete with mismatch repair factors that mediate heteroduplex rejection.

Source connections

Published article ↗

Explore related subjects

genetics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Chakraborty, U., Mackenroth, B., Alani, E. E.. 2019-01-13. Chromatin modifiers alter recombination between divergent DNA sequences. https://doi.org/10.1101/519397

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Integrated exome-transcriptome analysis of a schizophrenia case with an exceptionally low polygenic risk score

Schizophrenia liability reflects both common polygenic variation and rarer variants of larger effect. We investigated a post-mortem schizophrenia case (SZ07) with a schizophrenia polygenic risk score below the first percentile among ancestry-matched cases, asking whether individual-level genomic and transcriptomic analyses could help identify potentially novel schizophrenia-relevant variants. We used exome analysis with multiple variant-prediction tools to generate a panel of variants and corresponding candidate genes potentially implicated in the pathological process in SZ07. The prioritised variants were then assessed using RNA sequencing of three cortical regions. Of these, only an IZUMO4 splice-acceptor variant showed direct RNA-level support. Beyond variant-specific analyses, we characterised broader transcriptomic abnormalities in the SZ07 brain. Pathway analysis of gene-level expression deviations implicated innate immune processes, calcium signalling, synaptic biology, and axon remodelling. Notably, compared with conventional single-sample biological pathway analysis, the analysis we used showed only a weak association with neuronal specificity, suggesting their reduced sensitivity to the main axis of variation related to cellular composition in bulk brain tissue gene expression data. Although the candidate genes showed no significant pathway-level convergence, the broader transcriptomic profile revealed coherent biological alterations largely compatible with the documented history of cerebrovascular disease in SZ07. These results demonstrate how the integration of exome and transcriptome data at the individual level enables the formulation and constraint of hypotheses regarding patient-specific genetic features and their molecular consequences, while highlighting important limitations related to tissue composition, comorbidity, and the choice of reference cohort.

genetics↗

bioRxiv2026

A genetic screen to identify host factors required for commensal bacterial adherence to the gut epithelia

Bacterial adherence to gut epithelial cells likely involves host genetic components. We isolated a gut commensal bacterium, Lelliottia jeotgali, that can robustly colonize C. elegans through attachment to intestinal epithelial cells. Here, we developed a novel screen in C. elegans to identify host genes required for microbiome bacterial colonization. Using transgenic L. jeotgali strain expressing tdTomato, we conducted forward genetic screens in C. elegans to select for mutants that completely lost colonization. We identified multiple allelic mutations in five different C. elegans genes, termed knockout of Lelliottia adherence (kola) mutants, with a near complete loss of adherence. Each of kola-1-5 is uncharacterized and predicted to encode for a secreted or membrane-bound protein. We also identified gly-5, a GalNAc transferase that initiates O-linked glycosylation. Overall, we describe the first C. elegans screen to identify host factors that control microbiome bacterial colonization in the gut.

genetics↗

bioRxiv2026

Male-specific genome sequences for non-invasive sex identification in Nishikigoi (Cyprinus carpio)

Nishikigoi, ornamental cultivars of the common carp (Cyprinus carpio), are economically valuable aquaculture teleosts in which mature females command significantly higher market prices due to superior body conformation and coloration. Consequently, early and non-invasive sex identification is highly desirable for commercial breeding. Although sex determination in common carp follows an XX/XY system, sex-chromosome-specific markers and field-applicable diagnostic methods for Nishikigoi have remained limited. In this study, we conducted sequence-based bulked segregant analysis using whole-genome shotgun sequencing of female and male pools in Kohaku, a representative Nishikigoi lineage. We identified male-specific candidate contigs and successfully developed PCR-based male-specific markers. Validation across multiple Nishikigoi varieties and wild common carp demonstrated that primary primer pairs achieved high diagnostic accuracy. Comparative genomic analysis revealed that these candidate contigs mapped to the genomic region on chromosome 25B containing the male-determining gene Pangu, with the primary marker located in immediate physical proximity to the gene. To enable field diagnostics, we combined non-invasive epidermal mucus DNA extraction, loop-mediated isothermal amplification (LAMP), and chromatography-printed array strip (C-PAS) technology, establishing a rapid on-site detection workflow. Overall, this study provides highly reliable PCR markers associated with the sex-determination locus and establishes a non-invasive, field-applicable diagnostic platform to streamline commercial Nishikigoi breeding and sex-selected stock management.

genetics↗