Homologous recombination is a key evolutionary force that varies considerably across bacterial species. However, how the landscape of homologous recombination varies across genes and within individual genomes has only been studied in a few species. Here, we used Approximate Bayesian Computation to estimate the recombination rate along the genomes of 145 bacterial species. Our results show that homologous recombination varies greatly along bacterial genomes and shapes many aspects of genome architecture and evolution. The genomic landscape of recombination presents several key signatures: rates are highest near the origin of replication in most species, patterns of recombination generally appear symmetrical in both replichores ( replicational halves of circular chromosomes) and most species have genomic hotpots of recombination. Furthermore, many closely related species share conserved landscapes of recombination across orthologs indicating that recombination landscapes are conserved over significant evolutionary distances. We show evidence that recombination drives the evolution of GC-content through increasing the effectiveness of selection and not through biased gene conversion, thereby contributing to an ongoing debate. Finally, we demonstrate that the rate of recombination varies across gene function and that many hotspots of recombination are associated with adaptive and mobile regions often encoding genes involved in pathogenicity.
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http://dx.doi.org/10.1101/2024.05.31.596828 | DOI Listing |
Cancer Res
January 2025
INSERM U1194, Montpellier Cedex 05, Occitanie, France.
BRCA1 deficiency is observed in approximately 25% of triple-negative breast cancer (TNBC). BRCA1, a key player of homologous recombination (HR) repair, is also involved in stalled DNA replication fork protection and repair. Here, we investigated the sensitivity of BRCA1-deficient TNBC models to the frequently used replication chain terminator gemcitabine, which does not directly induce DNA breaks.
View Article and Find Full Text PDFInt J Gynecol Cancer
January 2025
Fudan University Shanghai Cancer Center, Department of Gynecologic Oncology, Shanghai, China; Fudan University, Shanghai Medical College, Department of Oncology, Shanghai, China. Electronic address:
Objective: Homologous recombination deficiency assays, guiding treatment of poly (adenosine diphosphate ribose) polymerase inhibitors, are increasingly applied in clinics. This study aimed to evaluate the predictive performance of homologous recombination deficiency status at genomic and functional perspective on the efficacy of platinum-based chemotherapy in ovarian cancer.
Methods: Between 2016 and 2019, 134 patients with high-grade ovarian cancer were retrospectively analyzed.
BJUI Compass
January 2025
Division of Medical Oncology A Policlinico Umberto I Rome Italy.
Background: We present a systematic review and meta-analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor-targeted agent (ARTA) in first- and second-line settings.
Methods: Primary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild-type (HRR-), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second-line setting is also explored.
Resistance to radiotherapy remains a critical barrier in treating colorectal cancer (CRC), particularly in cases of locally advanced rectal cancer (LARC). To identify key kinases involved in CRC radioresistance, we employed a kinase-targeted CRISPR-Cas9 library screen. This approach aimed to identify potential kinase inhibitors as radiosensitizers.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Laboratory of Genome Regeneration, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo113-0032, Japan.
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