Meiosis is an essential cell-division process for ensuring genetic diversity across generations. Meiotic recombination ensures the accuracy of genetic interchange between homolous chromosomes and segregation of parental alleles. Programmed DNA double-strand breaks (DSBs), catalyzed by the evolutionarily conserved topoisomerase VIA (a subunit of the archaeal type II DNA topoisomerase)-like enzyme Spo11 and several other factors, is a distinctive feature of meiotic recombination initiation. The meiotic DSB formation and its regulatory mechanisms are similar among species, but certain aspects are distinct. In this review, we introduced the cumulative knowledge of the plant proteins crucial for meiotic DSB formation and technical advances in DSB detection. We also summarized the genome-wide DSB hotspot profiles for different model organisms. Moreover, we highlighted the classical views and recent advances in our knowledge of the regulatory mechanisms that ensure the fidelity of DSB formation, such as multifaceted kinase-mediated phosphorylation and the consequent high-dimensional changes in chromosome structure. We provided an overview of recent findings concerning DSB formation, distribution and regulation, all of which will help us to determine whether meiotic DSB formation is evolutionarily conserved or varies between plants and other organisms.
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http://dx.doi.org/10.3390/ijms20194718 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Immunology and Microbiology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510000, China.
The LIM-domain-only protein LMO2 interacts with LDB1 in context-dependent multiprotein complexes and plays key roles in erythropoiesis and T cell leukemogenesis, but whether they have any roles in B cells is unclear. Through a CRISPR/Cas9-based loss-of-function screening, we identified LMO2 and LDB1 as factors for class switch recombination (CSR) in murine B cells. LMO2 contributes to CSR at least in part by promoting end joining of DNA double-strand breaks (DSBs) and inhibiting end resection.
View Article and Find Full Text PDFMol Med
January 2025
Research Institute, National Cancer Center, Goyang-Si, Gyeonggi-Do, 10408, Republic of Korea.
Background: Double-strand breaks (DSBs) are primarily repaired through non-homologous end joining (NHEJ) and homologous recombination (HR). Given that DSBs are highly cytotoxic, PARP inhibitors (PARPi), a prominent class of anticancer drugs, are designed to target tumors with HR deficiency (HRD), such as those harboring BRCA mutations. However, many tumor cells acquire resistance to PARPi, often by restoring HR in HRD cells through the inactivation of NHEJ.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Department of Biomedical Sciences (DSB), Institute of Experimental Endocrinology and Oncology "G. Salvatore" (IEOS), National Research Council (CNR), Naples, Italy.
The GC (Golgi complex) plays a pivotal role in the trafficking and sorting of proteins and lipids until they reach their final destination. Additionally, the GC acts as a signalling hub to regulate a multitude of cellular processes, including cell polarity, motility, apoptosis, DNA repair and cell division. In light of these crucial roles, the GC has garnered increasing attention, particularly given the evidence that a dysregulation of GC-regulated signalling pathways may contribute to the onset of various pathological conditions.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Hematopoietic Biology & Malignancy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cells undergo tens of thousands of DNA-damaging events each day. Defects in repairing double-stranded breaks (DSBs) can lead to genomic instability, contributing to cancer, genetic disorders, immunological diseases, and developmental defects. Cohesin, a multi-subunit protein complex, plays a crucial role in both chromosome organization and DNA repair by creating architectural loops through chromatin extrusion.
View Article and Find Full Text PDFNat Cell Biol
January 2025
Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.
Double-strand breaks (DSBs) can initiate mitotic catastrophe, a complex oncosuppressive phenomenon characterized by cell death during or after cell division. Here we unveil how cell cycle-regulated DSB repair guides disparate cell death outcomes through single-cell analysis of extended live imaging. Following DSB induction in S or G2, passage of unresolved homologous recombination intermediates into mitosis promotes non-immunogenic intrinsic apoptosis in the immediate attempt at cell division.
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