Meiotic crossing over is essential for the segregation of homologous chromosomes. The formation and distribution of meiotic crossovers (COs), which are initiated by the formation of double-strand break (DSB), are tightly regulated to ensure at least one CO per bivalent. One type of CO control, CO homeostasis, maintains a consistent level of COs despite fluctuations in DSB numbers. Here, we analyzed the localization of proteins involved in meiotic recombination in budding yeast hypomorphic mutants which show different levels of DSBs. The number of cytological foci with recombinases, Rad51 and Dmc1, which mark single-stranded DNAs at DSB sites is proportional to the DSB numbers. Among the pro-CO factor, ZMM/SIC proteins, the focus number of Zip3, Mer3, or Spo22/Zip4, was linearly proportional to reduced DSBs in the mutant. In contrast, foci of Msh5, a component of the MutSγ complex, showed a non-linear response to reduced DSBs. We also confirmed the homeostatic response of COs by genetic analysis of meiotic recombination in the mutants and found a chromosome-specific homeostatic response of COs. Our study suggests that the homeostatic response of the Msh5 assembly to reduced DSBs was genetically distinct from that of the Zip3 assembly for CO control.
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http://dx.doi.org/10.3389/fcell.2023.1170689 | DOI Listing |
Biomedicines
January 2025
Department of Hematology and Oncology, University Cancer Center Schleswig-Holstein (UCCSH), University Hospital Schleswig-Holstein, 23562 Lübeck, Germany.
: GFI1-36N represents a single-nucleotide polymorphism (SNP) of the zinc finger protein Growth Factor Independence 1 (GFI1), in which the amino acid serine (S) is replaced by asparagine (N). The presence of the gene variant is associated with a reduced DNA repair capacity favoring myeloid leukemogenesis and leads to an inferior prognosis of acute myeloid leukemia (AML) patients. However, the underlying reasons for the reduced DNA repair capacity in leukemic cells are largely 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 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 PDFInt J Mol Sci
December 2024
College of Life Sciences, Hebei University, Baoding 071002, China.
Bovine herpesvirus 1 (BoHV-1) productive infection induces the generation of DNA double-strand breaks (DSBs), which may consequently lead to cell apoptosis. In response to DSBs, the DNA damage repair-related protein 53BP1 is recruited to the sites of DSBs, leading to the formation of 53BP1foci, which are crucial for the repair of damaged DNA and maintaining genomic integrity by repairing DSBs. In this study, we discovered that HMGA1 may play a significant role in counteracting virus infection-induced DNA damage, as the siRNA-mediated knockdown of HMGA1 protein expression or inhibition of HMGA1 activity by the chemical inhibitor Netropsin uniformly exacerbates the DNA damage induced by BoHV-1 productive infection.
View Article and Find Full Text PDFGenes Cells
January 2025
School of Science and Technology, Gunma University, Kiryu, Japan.
Sulforaphane (SFN), an isothiocyanate found in plants of the Brassicaceae family, possesses antioxidant, apoptosis-inducing, and radiosensitizing effects. As one of the mechanisms of cytotoxicity by SFN, SFN has been suggested to be involved in the induction of DNA damage and inhibition of DNA repair. Recently, we reported on the potency of SFN in inducing single-ended double-strand breaks (DSBs) that are caused by the collision of replication forks with single-strand breaks (SSBs).
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