A5091610535- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Carcinogens and Genotoxicity Assessment
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Malaria Research and Control
- Neurobiology and Insect Physiology Research
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Cancer-related Molecular Pathways
- Plant Genetic and Mutation Studies
- Mosquito-borne diseases and control
- RNA Research and Splicing
- interferon and immune responses
- Cardiac Arrhythmias and Treatments
- Invertebrate Immune Response Mechanisms
- DNA and Nucleic Acid Chemistry
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Proteomics Techniques and Applications
- Plant Disease Resistance and Genetics
- Mycotoxins in Agriculture and Food
- Traditional and Medicinal Uses of Annonaceae
- Heart rate and cardiovascular health
- Insect Utilization and Effects
- Cancer therapeutics and mechanisms
University of North Carolina at Charlotte
2018-2025
Kyoto University
2005-2023
Shizuoka General Hospital
2022
The University of Texas MD Anderson Cancer Center
2013-2021
The University of Texas Health Science Center at Houston
2021
University of Houston
2014
Japan Society for the Promotion of Science
2013
Waseda University
2012
Ollscoil na Gaillimhe – University of Galway
2012
Kanazawa University
2012
Although a defect in the DNA polymerase POLQ leads to ionizing radiation sensitivity mammalian cells, relevant enzymatic pathway has not been identified. Here we define specific mechanism by which restricts harmful instability. Our experiments show that Polq-null murine cells are selectively hypersensitive strand breaking agents, and damage resistance requires activity of POLQ. Using break end joining assay monitored repair ends with long 3' single-stranded overhangs. End events retaining...
Article22 May 2018Open Access Source DataTransparent process FAM35A associates with REV7 and modulates DNA damage responses of normal BRCA1-defective cells Junya Tomida Corresponding Author [email protected] orcid.org/0000-0002-0813-5757 Department Epigenetics & Molecular Carcinogenesis, The University Texas MD Anderson Cancer Center, Smithville, TX, USA Search for more papers by this author Kei-ichi Takata Sarita Bhetawal Maria D Person Proteomics Facility, at Austin, Hsueh-Ping Chao Dean G...
When a replicative DNA polymerase (Pol) is stalled by damaged DNA, "polymerase switch" recruits specialized translesion synthesis (TLS) polymerase(s) to sites of damage. Mammalian cells have several TLS polymerases, including the four Y-family enzymes (Poleta, Poliota, Polkappa and REV1) that share multiple primary sequence motifs, but show preferential bypass different lesions. REV1 interacts with Poleta, therefore appears play central role during in vivo. Here we investigated molecular...
The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and suppression carcinogenesis. A key FA protein, FANCD2, monoubiquitinated accumulates chromatin response to DNA interstrand crosslinks (ICLs), where it coordinates repair through mechanisms that are still poorly understood. Here, we report CtIP protein directly interacts with FANCD2. region spanning amino acids 166 273 monoubiquitination FANCD2 both essential for FANCD2-CtIP interaction...
Abstract Mammalian HELQ is a 3′–5′ DNA helicase with strand displacement activity. Here we show that participates in pathway of resistance to interstrand crosslinks (ICLs). Genetic disruption human cells enhances cellular sensitivity and chromosome radial formation by the ICL-inducing agent mitomycin C (MMC). A significant fraction MMC independent Fanconi anaemia pathway. Sister chromatid exchange frequency UV radiation or topoisomerase inhibitors unaltered. Proteomic analysis reveals...
R‐loops, which consist of DNA : RNA hybrids and displaced single‐strand , are a major threat to genome stability. We have previously reported that key Fanconi anemia protein, FANCD 2, accumulates on large fragile genes during mild replication stress in manner depending R‐loops. In this study, we found 2 suppresses R‐loop levels. Furthermore, identified interactions with processing factors, including hn RNP U DDX 47. Our data suggest R‐loops chromatin, recruits these factors thereby promotes...
Abstract ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage. This event also causes phosphorylation Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination key repair factor FANCD2 by FA core E3 ligase complex, thereby promoting this central pathway which permits to be restarted. However, interplay between and has been unclear. In study, we present evidence that their action is directly linked, gaining insights into relationship in a...
DNA polymerase zeta (pol ) is exceptionally important for controlling mutagenesis and genetic instability.REV3L comprises the catalytic subunit, while REV7 (MAD2L2) considered an accessory subunit.However, it has not been established that role of in damage tolerance necessarily connected with mammalian pol , there accumulating evidence REV3L have independent functions.Analysis hampered by difficulties expression cells, lack a functional complementation system.Here, we report interacts...
When DNA replication is stalled at sites of damage, a cascade responses activated in the cell to halt cycle progression and promote repair. A pathway initiated by kinase Ataxia teleangiectasia Rad3 related (ATR) its partner ATR interacting protein (ATRIP) plays an important role this response. The Fanconi anemia (FA) also following genomic stress, defects cause cancer-prone hematologic disorder humans. Little known about how these two pathways are coordinated. We report here that cellular...
DNA polymerase ζ (pol ζ) is exceptionally important for maintaining genome stability. Inactivation of the Rev3l gene encoding catalytic subunit causes a high frequency chromosomal breaks, followed by lethality in mouse embryos and primary cells. Yet it not known whether activity pol specifically essential, as large REV3L protein also serves multiprotein scaffold translesion synthesis via multiple conserved structural domains. We report that cDNA rescues genomic instability damage sensitivity...
Significance Human dietary exposures to foods contaminated with fungi that synthesize aflatoxins present major health concerns and are associated increased risk of hepatocellular carcinomas. Previous biochemical analyses revealed a prominent role for DNA polymerase ζ in replication bypass mutagenesis the long-lived aflatoxin adduct. This investigation reveals an essential cell survival after exposure limits aflatoxin-induced genomic instability nuclear defects.
The DNA polymerase zeta (Polζ) plays a critical role in bypassing damage. REV3L, the catalytic subunit of Polζ, is also essential mouse embryonic development and cell proliferation for reasons that remain incompletely understood. In this study, we reveal REV3L protein interacts with heterochromatin components including repressive histone marks localizes pericentromeric regions through direct interaction HP1 dimer. We demonstrate Polζ/REV3L ensures progression replication forks...
SUMMARY Integration of DNA replication with repair, cell cycle progression, and other biological processes is crucial for preserving genome stability fundamentally important all life. Ataxia-telangiectasia mutated RAD3-related (ATR) its partner ATR-interacting protein (ATRIP) function as a critical proximal sensor transducer the Damage Response (DDR). Several ATR substrates, including p53 CHK1, are coordination phase transitions, transcription, repair when cells sustain damage. While much...
Many proteins involved in DNA replication and repair undergo post-translational modifications such as phosphorylation ubiquitylation. Proliferating cell nuclear antigen (PCNA; a homotrimeric protein that encircles double-stranded to function sliding clamp for polymerases) is monoubiquitylated by the RAD6-RAD18 complex further polyubiquitylated RAD5-MMS2-UBC13 response various DNA-damaging agents. PCNA mono- polyubiquitylation activate an error-prone translesion synthesis pathway error-free...
Polζ, a DNA polymerase specialized for translesion synthesis (TLS), is comprised of two subunits, the REV3 catalytic subunit and REV7 accessory subunit. The human (hREV7) protein known to interact with hREV3, hREV1 (another TLS protein) some other proteins such as ADAM9 (a disintegrin metalloprotease) ELK-1 (an Ets-like transcription factor). hREV7 alternatively termed hMAD2L2, because its primary sequence shows 26% identity that hMAD2 plays crucial roles in spindle assembly checkpoint (SAC)...
Histone H3 methylation on Lys4 (H3K4me) is associated with active gene transcription in all eukaryotes. In Saccharomyces cerevisiae , Set1 the sole lysine methyltransferase required for mono-, di-, and trimethylation of this site. Although H3K4me3 linked to expression, whether H3K4 regulates other cellular processes, such as mitosis, less clear. Here we show that both mutants display a benomyl resistance phenotype requires components spindle assembly checkpoint (SAC), including Bub3 Mad2....
In mammalian cells, specialized DNA polymerase ζ (pol ζ) contributes to genomic stability during normal replication. Disruption of the catalytic subunit Rev3l is toxic and results in constitutive chromosome damage, including micronuclei. As manifestations this stress are unknown, we examined transcriptome pol ζ-defective cells by RNA sequencing (RNA-seq). Expression 1,117 transcripts altered ≥4-fold Rev3l-disrupted with a pattern consistent an induction innate immune response. Increased...
REV7 is an abundant, multifunctional protein that a known factor in cell cycle regulation and several key DNA repair pathways including Trans-Lesion Synthesis (TLS), the Fanconi Anemia (FA) pathway, Double-Strand Break (DSB) pathway choice. Thus far, no direct role has been studied for damage response (DDR) signaling pathway. Here we describe novel function DSB-induced p53 signaling. We show binds directly to block ATM-dependent Ser15 phosphorylation. also report involved destabilization of...
ABSTRACT In order to exploit the specific vulnerabilities of tumors, it is urgent identify basis associated defects in genome maintenance. One unsolved problem mechanism inhibition processing DNA double-strand break repair by REV7 and its influence on pathways. We searched for REV7-associated proteins human cells found FAM35A, a protein previously unknown function. By analyzing FAM35A sequence we discovered that has an unstructured N-terminal region C-terminal harboring three OB-fold domains...
Background Various species, e.g., Caenorhabditis elegans, Drosophila melanogaster, and mice, have been used to explore the mechanisms of action general anesthetics in vivo. The authors isolated a mutant, ethas311, that was hypersensitive diethylether characterized calreticulin (crc) gene as candidate altered anesthetic sensitivity. Methods Molecular analysis crc included cloning sequencing cDNA, Northern blotting, situ hybridization accomplish function its mutation. For phenotype assay, 50%...
DNA polymerase ν (POLN) is one of 16 polymerases encoded in vertebrate genomes. It important to determine its gene expression patterns, biological roles, and biochemical activities. By quantitative analysis mRNA expression, we found that POLN from the zebrafish Danio rerio expressed predominantly testis. not detectably embryos or mouse embryonic stem cells. Consistent with this, injection POLN-specific morpholino antisense oligonucleotides did interfere development. Analysis transcripts...