ATP-dependent chromatin remodeling complexes have been shown to participate in DNA replication in addition to transcription and DNA repair. However, the mechanisms of their involvement in DNA replication remain unclear. Here, we reveal a specific function of the yeast INO80 chromatin remodeling complex in the DNA damage tolerance pathways. Whereas INO80 is necessary for the resumption of replication at forks stalled by methyl methane sulfonate (MMS), it is not required for replication fork collapse after treatment with hydroxyurea (HU). Mechanistically, INO80 regulates DNA damage tolerance during replication through modulation of PCNA (proliferating cell nuclear antigen) ubiquitination and Rad51-mediated processing of recombination intermediates at impeded replication forks. Our findings establish a mechanistic link between INO80 and DNA damage tolerance pathways, indicating that chromatin remodeling is important for accurate DNA replication.
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http://dx.doi.org/10.1038/nsmb.1686 | DOI Listing |
Viruses
December 2024
Division of Virology, ICMR-National Institute of Translational Virology and AIDS Research, Pune 411026, MH, India.
Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are the only members of the gamma(γ) herpesviruses, are oncogenic viruses that significantly contribute to the development of various human cancers, such as Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, Kaposi's sarcoma, and primary effusion lymphoma. Oncogenesis triggered by γ-herpesviruses involves complex interactions between viral genetics, host cellular mechanisms, and immune evasion strategies. At the genetic level, crucial viral oncogenes participate in the disruption of cell signaling, leading to uncontrolled proliferation and inhibition of apoptosis.
View Article and Find Full Text PDFViruses
November 2024
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Kaposi's sarcoma-associated herpesvirus (KSHV), a γ-herpesvirus, is predominantly associated with Kaposi's sarcoma (KS) as well as two lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). Like other herpesviruses, KSHV employs two distinct life cycles: latency and lytic replication. To establish a lifelong persistent infection, KSHV has evolved various strategies to manipulate the epigenetic machinery of the host.
View Article and Find Full Text PDFThe ARID1A gene, frequently mutated in cancer, encodes the AT-rich interactive domain-containing protein 1A, a key component of the chromatin remodeling SWI/SNF complex. The ARID1A protein features a conserved DNA-binding domain (ARID domain) of approximately 100 residues crucial for its function. Despite the frequency of mutations, the impact on ARID1A's stability and contribution to cancer progression remains unclear.
View Article and Find Full Text PDFStarvation, intermittent fasting and exercise, all of which are recommended lifestyle modifiers share a common metabolic signature, ketogenesis to generate the ketone bodies, predominantly β-hydroxybutyrate. β-hydroxybutyrate exerts beneficial effects across various contexts, preventing or mitigating disease. We hypothesized that these dynamic health benefits of β-hydroxybutyrate might stem from its ability to regulate genome architecture through chromatin remodeling via histone β-hydroxybutyrylation, thereby influencing the transcriptome.
View Article and Find Full Text PDFBackground: Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants, and more than 60% of children with ATRT die from their tumor. ATRT is associated with mutational inactivation/deletion of , a member of the SWI/SNF chromatin remodeling complex, suggesting that epigenetic events play a critical role in tumor development and progression. Moreover, disruption of SWI/SNF allows unopposed activity of epigenetic repressors, which contribute to tumorigenicity.
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