Meiotic recombination is a mandatory process for sexual reproduction. We identified a protein specifically implicated in meiotic homologous recombination that we named: meiosis specific with OB domain (MEIOB). This protein is conserved among metazoan species and contains single-strand DNA binding sites similar to those of RPA1. Our studies in vitro revealed that both recombinant and endogenous MEIOB can be retained on single-strand DNA. Those in vivo demonstrated the specific expression of Meiob in early meiotic germ cells and the co-localization of MEIOB protein with RPA on chromosome axes. MEIOB localization in Dmc1 (-/-) spermatocytes indicated that it accumulates on resected DNA. Homologous Meiob deletion in mice caused infertility in both sexes, due to a meiotic arrest at a zygotene/pachytene-like stage. DNA double strand break repair and homologous chromosome synapsis were impaired in Meiob (-/-) meiocytes. Interestingly MEIOB appeared to be dispensable for the initial loading of recombinases but was required to maintain a proper number of RAD51 and DMC1 foci beyond the zygotene stage. In light of these findings, we propose that RPA and this new single-strand DNA binding protein MEIOB, are essential to ensure the proper stabilization of recombinases which is required for successful homology search and meiotic recombination.
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http://dx.doi.org/10.1371/journal.pgen.1003784 | DOI Listing |
DNA Repair (Amst)
January 2025
Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program of Pathology, Federal University of Ceara, Fortaleza, Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program of Translational Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.
Myelodysplastic Neoplasm (MDS) is a cancer associated with aging, often leading to acute myeloid leukemia (AML). One of its hallmarks is hypermethylation, particularly in genes responsible for DNA repair. This study aimed to evaluate the methylation and mutation status of DNA repair genes (single-strand - XPA, XPC, XPG, CSA, CSB and double-strand - ATM, BRCA1, BRCA2, LIG4, RAD51) in MDS across three patient cohorts (Cohort A-56, Cohort B-100, Cohort C-76), using methods like pyrosequencing, real-time PCR, immunohistochemistry, and mutation screening.
View Article and Find Full Text PDFBio Protoc
January 2025
International Institute of Food Innovation Co., Ltd., Nanchang University, Nanchang, China.
PCR-based genome walking is one of the prevalent techniques implemented to acquire unknown flanking genomic DNAs. The worth of genome walking includes but is not limited to cloning full-length genes, mining new genes, and discovering regulatory regions of genes. Therefore, this technique has advanced molecular biology and related fields.
View Article and Find Full Text PDFExp Mol Med
January 2025
Section on DNA Repair, Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
RecQ helicases, highly conserved proteins with pivotal roles in DNA replication, DNA repair and homologous recombination, are crucial for maintaining genomic integrity. Mutations in RECQL4 have been associated with various human diseases, including Rothmund-Thomson syndrome. RECQL4 is involved in regulating major DNA repair pathways, such as homologous recombination and nonhomologous end joining (NHEJ).
View Article and Find Full Text PDFNat Commun
January 2025
Mechanisms, Biomarkers and Models Section - Genome Stability Group, Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299 - 00161, Rome, Italy.
The WRN protein is vital for managing perturbed replication forks. Replication Protein A strongly enhances WRN helicase activity in specific in vitro assays. However, the in vivo significance of RPA binding to WRN has largely remained unexplored.
View Article and Find Full Text PDFACS Biomater Sci Eng
January 2025
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611, United States.
The complexation of nucleic acids and collagen forms a platform biomaterial greater than the sum of its parts. This union of biomacromolecules merges the extracellular matrix functionality of collagen with the designable bioactivity of nucleic acids, enabling advances in regenerative medicine, tissue engineering, gene delivery, and targeted therapy. This review traces the historical foundations and critical applications of DNA-collagen complexes and highlights their capabilities, demonstrating them as biocompatible, bioactive, and tunable platform materials.
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