Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays a critical role in many fundamental cellular processes. We recently reported that PP6 is essential for female fertility. Here, we report that PP6 is involved in meiotic recombination and that germ cell-specific deletion of PP6 by Stra8-Cre causes defective spermatogenesis. The PP6-deficient spermatocytes were arrested at the pachytene stage and defects in DSB repair and crossover formation were observed, indicating that PP6 facilitated meiotic double-stranded breaks (DSB) repair. Further investigations revealed that depletion of PP6 in the germ cells affected chromatin relaxation, which was dependent on MAPK pathway activity, consequently preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. Taken together, our results demonstrate that PP6 has an important role in meiotic recombination and male fertility.
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http://dx.doi.org/10.1038/s41418-019-0472-9 | DOI Listing |
J Clin Immunol
January 2025
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children´s Medical Center, Tehran University of Medical Sciences, 62 Qarib St., Keshavarz Blvd, Tehran, 14194, Iran.
Background: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.
View Article and Find Full Text PDFDNA Repair (Amst)
January 2025
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:
Proper chromatin remodeling is crucial for many cellular physiological processes, including the repair of DNA double-strand break (DSB). While the mechanism of DSB repair is well understood, the connection between chromatin remodeling and DSB repair remains incompletely elucidated. In this review, we aim to highlight recent studies demonstrating the close relationship between chromatin remodeling and DSB repair.
View Article and Find Full Text PDFPlant Physiol Biochem
January 2025
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup-si, Jeonbuk-do, 56212, Republic of Korea.
Argonaute (AGO) proteins are involved in gene expression and genome integrity during biotic and abiotic stress responses. AGO2 mediates double-strand break (DSB) repair in DNA damage response (DDR) induced by genotoxic stress. However, beyond DSB repair, the involvement of AGO proteins in DDR remains unknown.
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.
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