keyword
MENU ▼
Read by QxMD icon Read
search

Replication fork

keyword
https://www.readbyqxmd.com/read/29334356/p53-suppresses-mutagenic-rad52-and-pol%C3%AE-pathways-by-orchestrating-dna-replication-restart-homeostasis
#1
Sunetra Roy, Karl-Heinz Tomaszowski, Jessica W Luzwick, Soyoung Park, Jun Li, Maureen Murphy, Katharina Schlacher
Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell cycle arrest. Yet, replication-mediated genomic instability is integral to oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By delineating human and murine separation-of-function p53 alleles, we find that p53 null and gain-of-function (GOF) mutations exhibit defects in restart of stalled or damaged DNA replication forks driving genomic instability genetically separable from transcription activation. By assaying protein-DNA fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of MRE11 DNA replication restart nuclease...
January 15, 2018: ELife
https://www.readbyqxmd.com/read/29301856/rad9-53bp1-protects-stalled-replication-forks-from-degradation-in-mec1-atr-defective-cells
#2
Matteo Villa, Diego Bonetti, Massimo Carraro, Maria Pia Longhese
Nucleolytic processing by nucleases can be a relevant mechanism to allow repair/restart of stalled replication forks. However, nuclease action needs to be controlled to prevent overprocessing of damaged replication forks that can be detrimental to genome stability. The checkpoint protein Rad9/53BP1 is known to limit nucleolytic degradation (resection) of DNA double-strand breaks (DSBs) in both yeast and mammals. Here, we show that loss of the inhibition that Rad9 exerts on resection exacerbates the sensitivity to replication stress of Mec1/ATR-defective yeast cells by exposing stalled replication forks to Dna2-dependent degradation...
January 4, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29298824/mof-suppresses-replication-stress-and-contribute-to-resolution-of-stalled-replication-forks
#3
Dharmendra Kumar Singh, Raj K Pandita, Mayank Singh, Sharmistha Chakraborty, Shashank Hambarde, Deepti Ramnarain, Vijaya Charaka, Kazi Mokim Ahmed, Clayton R Hunt, Tej K Pandita
The hMOF protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription and the DNA damage response. MOF is essential for cell proliferation, however its role during replication and replicative stress is unknown. Here we demonstrate that cells depleted for MOF and under replicative stress induced by cisplatin, hydroxyurea or camptothecin have reduced survival, a higher frequency of S-phase specific chromosome damage and increased R-loop formation. MOF depletion decreased replication fork speed and, when combined with replicative stress, also increased stalled replication forks as well as new origin firing...
January 3, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29298091/lesion-bypass-and-the-reactivation-of-stalled-replication-forks
#4
Kenneth J Marians
Accurate transmission of the genetic information requires complete duplication of the chromosomal DNA each cell division cycle. However, the idea that replication forks would form at origins of DNA replication and proceed without impairment to copy the chromosomes has proven naive. It is now clear that replication forks stall frequently as a result of encounters between the replication machinery and template damage, slow-moving or paused transcription complexes, unrelieved positive superhelical tension, covalent protein-DNA complexes, and as a result of cellular stress responses...
January 3, 2018: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/29290612/removal-of-rtf2-from-stalled-replisomes-promotes-maintenance-of-genome-integrity
#5
Molly C Kottemann, Brooke A Conti, Francis P Lach, Agata Smogorzewska
The protection and efficient restart of stalled replication forks is critical for the maintenance of genome integrity. Here, we identify a regulatory pathway that promotes stalled forks recovery from replication stress. We show that the mammalian replisome component C20orf43/RTF2 (homologous to S. pombe Rtf2) must be removed for fork restart to be optimal. We further show that the proteasomal shuttle proteins DDI1 and DDI2 are required for RTF2 removal from stalled forks. Persistence of RTF2 at stalled forks results in fork restart defects, hyperactivation of the DNA damage signal, accumulation of single-stranded DNA (ssDNA), sensitivity to replication drugs, and chromosome instability...
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29290468/stabilization-of-reversed-replication-forks-by-telomerase-drives-telomere-catastrophe
#6
Pol Margalef, Panagiotis Kotsantis, Valerie Borel, Roberto Bellelli, Stephanie Panier, Simon J Boulton
Telomere maintenance critically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the end replication problem, and RTEL1, which dismantles DNA secondary structures at telomeres to facilitate replisome progression. Here, we establish that reversed replication forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rtel1-/- cells. Inhibiting telomerase recruitment to telomeres, but not its activity, or blocking replication fork reversal through PARP1 inhibition or depleting UBC13 or ZRANB3 prevents the rapid accumulation of dysfunctional telomeres in RTEL1-deficient cells...
December 27, 2017: Cell
https://www.readbyqxmd.com/read/29279302/genetic-evidence-for-roles-of-yeast-mitotic-cyclins-at-single-stranded-gaps-created-by-dna-replication
#7
Laurence Signon
Paused/stalled replication forks are major threats to genome integrity; unraveling the complex pathways that contribute to fork stability/restart is crucial. Experimentally, fork stalling is induced by growth in presence of hydroxyurea (HU), which depletes the pool of deoxynucleoside triphosphates (dNTPs) and slows down replication progression in yeast. Here, I report an epistasis analysis, based on sensitivity to HU, between CLB2, the principal mitotic cyclin gene in S. cerevisiae, and genes involved in fork stability and recombination...
December 26, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29262356/nanoscale-assembly-of-high-mobility-group-at-hook-2-protein-with-dna-replication-fork
#8
Natalie Krahn, Markus Meier, Vu To, Evan P Booy, Kevin McEleney, Joe D O'Neil, Sean A McKenna, Trushar R Patel, Jörg Stetefeld
High mobility group AT-hook 2 (HMGA2) protein is composed of three AT-hook domains. HMGA2 expresses at high levels in both embryonic stem cells and cancer cells, where it interacts with and stabilizes replication forks (RFs), resulting in elevated cell proliferation rates. In this study, we demonstrated that HMGA2 knockdown reduces cell proliferation. To understand the features required for interaction between HMGA2 and RFs, we studied the solution structure of HMGA2, free and in complex with RFs, using an integrated host of biophysical techniques...
December 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29261494/-g-quadruplex-key-controllers-of-human-genome-duplication
#9
Jérémy Poulet-Benedetti, Anne-Laure Valton, Marie-Noëlle Prioleau
The correct duplication of the human genome is under the control of a spatiotemporal program that determines where and when replication forks start. This regulation thus mainly operates on replication start sites named replication origins. During the S-phase, about 50 000 origins fire in one human cell. However, the normal or perturbed progression of replication forks also strongly impacts on replication. Recently, several studies have put forward the role of a noncanonical DNA structure, the G-quadruplex, in the control of genome duplication...
December 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29259108/replication-fork-convergence-at-termination-a-multistep-process
#10
Nina Y Yao, Mike E O'Donnell
No abstract text is available yet for this article.
December 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29249653/replication-stress-shapes-a-protective-chromatin-environment-across-fragile-genomic-regions
#11
Jeongkyu Kim, David Sturgill, Robin Sebastian, Simran Khurana, Andy D Tran, Garrett B Edwards, Alex Kruswick, Sandra Burkett, Eri K Hosogane, William W Hannon, Urbain Weyemi, William M Bonner, Karolin Luger, Philipp Oberdoerffer
Recent integrative epigenome analyses highlight the importance of functionally distinct chromatin states for accurate cell function. How these states are established and maintained is a matter of intense investigation. Here, we present evidence for DNA damage as an unexpected means to shape a protective chromatin environment at regions of recurrent replication stress (RS). Upon aberrant fork stalling, DNA damage signaling and concomitant H2AX phosphorylation coordinate the FACT-dependent deposition of macroH2A1...
December 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29247828/hypersensitivity-of-mouse-embryonic-fibroblast-cells-defective-for-dna-polymerases-%C3%AE-%C3%AE-and-%C3%AE%C2%BA-to-various-genotoxic-compounds-its-potential-for-application-in-chemical-genotoxic-screening
#12
Jun-Ichi Akagi, Masayuki Yokoi, Young-Man Cho, Takeshi Toyoda, Haruo Ohmori, Fumio Hanaoka, Kumiko Ogawa
Genotoxic agents cause modifications of genomic DNA, such as alkylation, oxidation, bulky adduct formation, and strand breaks, which potentially induce mutations and changes to the structure or number of genes. Majority of point mutations are generated during error-prone bypass of modified nucleotides (translesion DNA synthesis, TLS); however, when TLS fails, replication forks stalled at lesions eventually result in more lethal effects, formation of double-stranded breaks (DSBs). Here we compared sensitivities to various compounds among mouse embryonic fibroblasts derived from wild-type and knock-out mice lacking one of the three Y-family TLS DNA polymerases (Polη, Polι, and Polκ) or all of them (TKO)...
November 26, 2017: DNA Repair
https://www.readbyqxmd.com/read/29243303/genotoxic-and-mutagenic-properties-of-ni-and-nio-nanoparticles-investigated-by-comet-assay-%C3%AE-h2ax-staining-hprt-mutation-assay-and-toxtracker-reporter-cell-lines
#13
Emma Åkerlund, Francesca Cappellini, Sebastiano Di Bucchianico, Shafiqul Islam, Sara Skoglund, Remco Derr, Inger Odnevall Wallinder, Giel Hendriks, Hanna L Karlsson
Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. The aim of this study was to investigate genotoxicity and mutagenicity of Ni and NiO NPs and compare the effect to soluble Ni from NiCl2 . We employed different models; i.e., exposure of (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay and γ-H2AX staining); (2) six different mouse embryonic stem (mES) reporter cell lines (ToxTracker) that are constructed to exhibit fluorescence upon the induction of various pathways of relevance for (geno)toxicity and cancer; and (3) mES cells followed by mutagenicity testing (Hprt assay)...
December 15, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29234107/bulky-lesion-bypass-requires-dpo4-binding-in-distinct-conformations
#14
Pramodha S Liyanage, Alice R Walker, Alfonso Brenlla, G Andrés Cisneros, Louis J Romano, David Rueda
Translesion DNA synthesis is an essential process that helps resume DNA replication at forks stalled near bulky adducts on the DNA. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH) that can be metabolically activated to benzo[a]pyrene diol epoxide (BPDE), which then can react with DNA to form carcinogenic DNA adducts. Here, we have used single-molecule florescence resonance energy transfer (smFRET) experiments, classical molecular dynamics simulations, and nucleotide incorporation assays to investigate the mechanism by which the model Y-family polymerase, Dpo4, bypasses a (+)-cis-B[a]P-N 2-dG adduct in DNA...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234069/the-human-dna-glycosylases-neil1-and-neil3-excise-psoralen-induced-dna-dna-cross-links-in-a-four-stranded-dna-structure
#15
Peter R Martin, Sophie Couvé, Caroline Zutterling, Mustafa S Albelazi, Regina Groisman, Bakhyt T Matkarimov, Jason L Parsons, Rhoderick H Elder, Murat K Saparbaev
Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229671/h3s10ph-broadly-marks-early-replicating-domains-in-interphase-escs-and-shows-reciprocal-antagonism-with-h3k9me2
#16
Carol C L Chen, Preeti Goyal, Mohammad M Karimi, Marie H Abildgaard, Hiroshi Kimura, Matthew C Lorincz
Phosphorylation of histone H3 at serine 10 (H3S10ph) by Aurora kinases plays an important role in mitosis; however, H3S10ph also marks regulatory regions of inducible genes in interphase mammalian cells, implicating mitosis-independent functions. Using the fluorescent ubiquitin-mediated cell cycle indicator (FUCCI), we found that 30% of the genome in interphase mouse embryonic stem cells (ESCs) is marked with H3S10ph. H3S10ph broadly demarcates gene-rich regions in G1 and is positively correlated with domains of early DNA replication timing (RT) but negatively correlated with H3K9me2 and lamin-associated domains (LADs)...
December 11, 2017: Genome Research
https://www.readbyqxmd.com/read/29229598/cdkn2a-p16-deletion-in-head-and-neck-cancer-cells-is-associated-with-cdk2-activation-replication-stress-and-vulnerability-to-chk1-inhibition
#17
Mayur A Gadhikar, Jiexin Zhang, Li Shen, Xiayu Rao, Jing Wang, Mei Zhao, Nene N Kalu, Faye M Johnson, Lauren A Byers, John Heymach, Walter N Hittelman, Durga Udayakumar, Raj K Pandita, Tej K Pandita, Curtis R Pickering, Abena Redwood, Helen Piwnica-Worms, Katharina Schlacher, Mitchell J Frederick, Jeffrey N Myers
Checkpoint kinase inhibitors (CHKi) exhibit striking single agent activity in certain tumors, but the mechanisms accounting for hypersensitivity are poorly understood. We screened a panel of 49 established human head and neck squamous cell carcinoma (HNSCC) cell lines and report that nearly 20% are hypersensitive to CHKi monotherapy. Hypersensitive cells underwent early S-phase arrest at drug doses sufficient to inhibit greater than 90% of Chk1 activity. Reduced rate of DNA replication fork progression and chromosomal shattering were also observed, suggesting replication stress as a root causative factor in CHKi hypersensitivity...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29220651/replication-fork-reversal-players-and-guardians
#18
REVIEW
Annabel Quinet, Delphine Lemaçon, Alessandro Vindigni
Replication fork reversal is a rapidly emerging and remarkably frequent mechanism of fork stabilization in response to genotoxic insults. Here, we summarize recent findings that uncover key molecular determinants for reversed fork formation and describe how the homologous recombination factors BRCA1, BRCA2, and RAD51 protect these structures from extended nucleolytic degradation.
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29215009/the-end-joining-factor-ku-acts-in-the-end-resection-of-double-strand-break-free-arrested-replication-forks
#19
Ana Teixeira-Silva, Anissia Ait Saada, Julien Hardy, Ismail Iraqui, Marina Charlotte Nocente, Karine Fréon, Sarah A E Lambert
Replication requires homologous recombination (HR) to stabilize and restart terminally arrested forks. HR-mediated fork processing requires single stranded DNA (ssDNA) gaps and not necessarily double strand breaks. We used genetic and molecular assays to investigate fork-resection and restart at dysfunctional, unbroken forks in Schizosaccharomyces pombe. Here, we report that fork-resection is a two-step process regulated by the non-homologous end joining factor Ku. An initial resection mediated by MRN-Ctp1 removes Ku from terminally arrested forks, generating ~110 bp sized gaps obligatory for subsequent Exo1-mediated long-range resection and replication restart...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29209094/possible-function-of-the-second-recj-like-protein-in-stalled-replication-fork-repair-by-interacting-with-hef
#20
Mariko Nagata, Sonoko Ishino, Takeshi Yamagami, Jan-Robert Simons, Tamotsu Kanai, Haruyuki Atomi, Yoshizumi Ishino
RecJ was originally identified in Escherichia coli and plays an important role in the DNA repair and recombination pathways. Thermococcus kodakarensis, a hyperthermophilic archaeon, has two RecJ-like nucleases. These proteins are designated as GAN (GINS-associated nuclease) and HAN (Hef-associated nuclease), based on the protein they interact with. GAN is probably a counterpart of Cdc45 in the eukaryotic CMG replicative helicase complex. HAN is considered mainly to function with Hef for restoration of the stalled replication fork...
December 5, 2017: Scientific Reports
keyword
keyword
81326
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"