keyword
MENU ▼
Read by QxMD icon Read
search

Mus81

keyword
https://www.readbyqxmd.com/read/28369583/substrate-preference-of-gen-endonucleases-highlights-the-importance-of-branched-structures-as-dna-damage-repair-intermediates
#1
Stephanie P Bellendir, Danielle J Rognstad, Lydia P Morris, Grzegorz Zapotoczny, William G Walton, Matthew R Redinbo, Dale A Ramsden, Jeff Sekelsky, Dorothy A Erie
Human GEN1 and yeast Yen1 are endonucleases with the ability to cleave Holliday junctions (HJs), which are proposed intermediates in recombination. In vivo, GEN1 and Yen1 function secondarily to Mus81, which has weak activity on intact HJs. We show that the genetic relationship is reversed in Drosophila, with Gen mutants having more severe defects than mus81 mutants. In vitro, DmGen, like HsGEN1, efficiently cleaves HJs, 5΄ flaps, splayed arms, and replication fork structures. We find that the cleavage rates for 5΄ flaps are significantly higher than those for HJs for both DmGen and HsGEN1, even in vast excess of enzyme over substrate...
March 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28341648/dna-damage-tolerance-pathway-choice-through-uls1-modulation-of-srs2-sumoylation-in-saccharomyces-cerevisiae
#2
Karol Kramarz, Seweryn Mucha, Ireneusz Litwin, Anna Barg-Wojas, Robert Wysocki, Dorota Dziadkowiec
DNA damage tolerance and homologous recombination pathways function to bypass replication blocking lesions and ensure completion of DNA replication. However, inappropriate activation of these pathways may lead to increased mutagenesis or formation of deleterious recombination intermediates often leading to cell death or cancer formation in higher organisms. Posttranslational modifications of PCNA regulate the choice of repair pathways at replication forks. Its monoubiquitination favors translesion synthesis while polyubiquitination stimulates template switching...
March 24, 2017: Genetics
https://www.readbyqxmd.com/read/28327556/control-of-structure-specific-endonucleases-to-maintain-genome-stability
#3
REVIEW
Pierre-Marie Dehé, Pierre-Henri L Gaillard
Structure-specific endonucleases (SSEs) have key roles in DNA replication, recombination and repair, and emerging roles in transcription. These enzymes have specificity for DNA secondary structure rather than for sequence, and therefore their activity must be precisely controlled to ensure genome stability. In this Review, we discuss how SSEs are controlled as part of genome maintenance pathways in eukaryotes, with an emphasis on the elaborate mechanisms that regulate the members of the major SSE families - including the xeroderma pigmentosum group F-complementing protein (XPF) and MMS and UV-sensitive protein 81 (MUS81)-dependent nucleases, and the flap endonuclease 1 (FEN1), XPG and XPG-like endonuclease 1 (GEN1) enzymes - during processes such as DNA adduct repair, Holliday junction processing and replication stress...
May 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28318385/arsenic-induced-sumoylation-of-mus81-is-involved-in-regulating-genomic-stability
#4
Liyan Hu, Feikun Yang, Lou Lu, Wei Dai
Chronic environmental exposure to metal toxicants such as chromium and arsenic is closely related to the development of several types of common cancers. Genetic and epigenetic studies in the past decade reveal that post-translational modifications of histones play a role in metal carcinogenesis. However, exact molecular mechanisms of metal carcinogenesis remain to be elucidated. In this study we found that As2O3, an environmental metal toxicant, upregulated overall modifications of many cellular proteins by SUMO2/3...
April 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28315832/modulating-crossover-frequency-and-interference-for-obligate-crossovers-in-saccharomyces-cerevisiae-meiosis
#5
Parijat Chakraborty, Ajith V Pankajam, Gen Lin, Abhishek Dutta, Krishnaprasad G Nandanan, Manu M Tekkedil, Akira Shinohara, Lars M Steinmetz, Nishant K Thazath
Meiotic crossover frequencies show wide variation among organisms. But most organisms maintain at least one crossover per homolog pair (obligate crossover). In Saccharomyces cerevisiae, previous studies have shown crossover frequencies are reduced in the mismatch repair related mutant mlh3Δ and enhanced in a meiotic checkpoint mutant pch2Δ by up to two-fold at specific chromosomal loci, but both mutants maintain high spore viability. We analyzed meiotic recombination events genome-wide in mlh3Δ, pch2Δ and mlh3Δ pch2Δ mutants to test the effect of variation in crossover frequency on obligate crossovers...
March 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28291626/mus81-knockdown-sensitizes-colon-cancer-cells-to-chemotherapeutic-drugs-by-activating-chk1-pathway
#6
Fan Wu, Shu-Chao Su, Guo-Qian Tan, Lun Yan, Ting-Yue Li, Hao-Lu Zhang, Ji-Shang Yu, Bai-Lin Wang
PURPOSE: The inhibition of Mus81, a critical DNA repair gene, is recently related to the chemosensitivity of several human cancer cells such as hepatocellular carcinoma (HCC) cells. However, the role of Mus81 knockdown in chemotherapy response of colon cancer cells remains largely unknown. METHODS AND MATERIALS: The effects of Mus81 knockdown by lentivirus-mediated short hairpin RNA in sensitivity of HCT116 and LS180 colon cancer cell lines to four therapeutic drugs, including cisplatin (CDDP), were evaluated by MTT assay as well as a mouse model...
March 10, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28290553/slx4-prevents-gen1-dependent-dsbs-during-dna-replication-arrest-under-pathological-conditions-in-human-cells
#7
Eva Malacaria, Annapaola Franchitto, Pietro Pichierri
SLX4 is a versatile protein serving as docking for multiple structure-specific endonucleases during DNA repair, however, little is known about its function at demised replication forks. Using RNAi or FA-P cells complemented with SLX4 mutants that abrogate interaction with MUS81 or SLX1, we show that SLX4 cooperates with MUS81 to introduce DSBs after replication stress but also counteracts pathological targeting of demised forks by GEN1. Such unexpected function of SLX4 is unrelated to interaction with endonucleases, but concerns the physical presence of the protein...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257701/the-smx-dna-repair-tri-nuclease
#8
Haley D M Wyatt, Rob C Laister, Stephen R Martin, Cheryl H Arrowsmith, Stephen C West
The efficient removal of replication and recombination intermediates is essential for the maintenance of genome stability. Resolution of these potentially toxic structures requires the MUS81-EME1 endonuclease, which is activated at prometaphase by formation of the SMX tri-nuclease containing three DNA repair structure-selective endonucleases: SLX1-SLX4, MUS81-EME1, and XPF-ERCC1. Here we show that SMX tri-nuclease is more active than the three individual nucleases, efficiently cleaving replication forks and recombination intermediates...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28096179/dbf4-dependent-kinase-and-the-rtt107-scaffold-promote-mus81-mms4-resolvase-activation-during-mitosis
#9
Lissa N Princz, Philipp Wild, Julia Bittmann, F Javier Aguado, Miguel G Blanco, Joao Matos, Boris Pfander
DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner...
March 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28049740/resolvase-osgen1-mediates-dna-repair-by-homologous-recombination
#10
Chong Wang, James D Higgins, Yi He, Pingli Lu, Dabing Zhang, Wanqi Liang
Yen1/GEN1 are canonical Holliday junction resolvases that belong to the RAD2/XPG family. In eukaryotes, such as budding yeast, mice, worms, and humans, Yen1/GEN1 work together with Mus81-Mms4/MUS81-EME1 and Slx1-Slx4/SLX1-SLX4 in DNA repair by homologous recombination to maintain genome stability. In plants, the biological function of Yen1/GEN1 remains largely unclear. In this study, we characterized the loss of function mutants of OsGEN1 and OsSEND1, a pair of paralogs of Yen1/GEN1 in rice (Oryza sativa). We first investigated the role of OsGEN1 during meiosis and found a reduction in chiasma frequency by ∼6% in osgen1 mutants, compared to the wild type, suggesting a possible involvement of OsGEN1 in the formation of crossovers...
February 2017: Plant Physiology
https://www.readbyqxmd.com/read/27997828/a-mechanism-for-controlled-breakage-of-under-replicated-chromosomes-during-mitosis
#11
Heike Duda, Meret Arter, Jiradet Gloggnitzer, Federico Teloni, Philipp Wild, Miguel G Blanco, Matthias Altmeyer, Joao Matos
While DNA replication and mitosis occur in a sequential manner, precisely how cells maintain their temporal separation and order remains elusive. Here, we unveil a double-negative feedback loop between replication intermediates and an M-phase-specific structure-selective endonuclease, MUS81-SLX4, which renders DNA replication and mitosis mutually exclusive. MUS81 nuclease is constitutively active throughout the cell cycle but requires association with SLX4 for efficient substrate targeting. To preclude toxic processing of replicating chromosomes, WEE1 kinase restrains CDK1 and PLK1-mediated MUS81-SLX4 assembly during S phase...
December 19, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27984745/rad52-facilitates-mitotic-dna-synthesis-following-replication-stress
#12
Rahul Bhowmick, Sheroy Minocherhomji, Ian D Hickson
Homologous recombination (HR) is necessary to counteract DNA replication stress. Common fragile site (CFS) loci are particularly sensitive to replication stress and undergo pathological rearrangements in tumors. At these loci, replication stress frequently activates DNA repair synthesis in mitosis. This mitotic DNA synthesis, termed MiDAS, requires the MUS81-EME1 endonuclease and a non-catalytic subunit of the Pol-delta complex, POLD3. Here, we examine the contribution of HR factors in promoting MiDAS in human cells...
December 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27939696/stc2-as-a-novel-mediator-for-mus81-dependent-proliferation-and-survival-in-hepatocellular-carcinoma
#13
Fan Wu, Ting-Yue Li, Shu-Chao Su, Ji-Shang Yu, Hao-Lu Zhang, Guo-Qian Tan, Jian-Wei Liu, Bai-Lin Wang
Methyl methansulfonate and UV sensitive gene clone 81 (Mus81) is a critical DNA repair gene that has been implicated in development of several cancers including hepatocellular carcinoma (HCC). However, whether Mus81 can affect proliferation and survival of HCC remains unknown. In the present study, we demonstrated that the knockdown of Mus81 was associated with suppressed proliferation and elevated apoptosis of HCC cells in vitro and in vivo. Multilayered screenings, including DNA microarray, high content screen, and real-time PCR validation, identified STC2 as a proliferation-facilitating gene significantly down-regulated in HCC cells upon Mus81 knockdown...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27918542/the-role-of-break-induced-replication-in-large-scale-expansions-of-cag-n-ctg-n-repeats
#14
Jane C Kim, Samantha T Harris, Teresa Dinter, Kartik A Shah, Sergei M Mirkin
Expansions of (CAG)n/(CTG)n trinucleotide repeats are responsible for over a dozen neuromuscular and neurodegenerative disorders. Large-scale expansions are commonly observed in human pedigrees and may be explained by iterative small-scale events such as strand slippage during replication or repair DNA synthesis. Alternatively, a distinct mechanism may lead to a large-scale repeat expansion as a single step. To distinguish between these possibilities, we developed a novel experimental system specifically tuned to analyze large-scale expansions of (CAG)n/(CTG)n repeats in Saccharomyces cerevisiae...
January 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27806301/meiotic-nuclear-oscillations-are-necessary-to-avoid-excessive-chromosome-associations
#15
Mariola R Chacón, Petrina Delivani, Iva M Tolić
Pairing of homologous chromosomes is a crucial step in meiosis, which in fission yeast depends on nuclear oscillations. However, how nuclear oscillations help pairing is unknown. Here, we show that homologous loci typically pair when the spindle pole body is at the cell pole and the nucleus is elongated, whereas they unpair when the spindle pole body is in the cell center and the nucleus is round. Inhibition of oscillations demonstrated that movement is required for initial pairing and that prolonged association of loci leads to mis-segregation...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27779184/replication-intermediates-that-escape-dna2-activity-are-processed-by-holliday-junction-resolvase-yen1
#16
Gizem Ölmezer, Maryna Levikova, Dominique Klein, Benoît Falquet, Gabriele Alessandro Fontana, Petr Cejka, Ulrich Rass
Cells have evolved mechanisms to protect, restart and repair perturbed replication forks, allowing full genome duplication, even under replication stress. Interrogating the interplay between nuclease-helicase Dna2 and Holliday junction (HJ) resolvase Yen1, we find the Dna2 helicase activity acts parallel to homologous recombination (HR) in promoting DNA replication and chromosome detachment at mitosis after replication fork stalling. Yen1, but not the HJ resolvases Slx1-Slx4 and Mus81-Mms4, safeguards chromosome segregation by removing replication intermediates that escape Dna2...
October 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27697832/rad51-and-rad54-promote-noncrossover-recombination-between-centromere-repeats-on-the-same-chromatid-to-prevent-isochromosome-formation
#17
Atsushi T Onaka, Naoko Toyofuku, Takahiro Inoue, Akiko K Okita, Minami Sagawa, Jie Su, Takeshi Shitanda, Rei Matsuyama, Faria Zafar, Tatsuro S Takahashi, Hisao Masukata, Takuro Nakagawa
Centromeres consist of DNA repeats in many eukaryotes. Non-allelic homologous recombination (HR) between them can result in gross chromosomal rearrangements (GCRs). In fission yeast, Rad51 suppresses isochromosome formation that occurs between inverted repeats in the centromere. However, how the HR enzyme prevents homology-mediated GCRs remains unclear. Here, we provide evidence that Rad51 with the aid of the Swi/Snf-type motor protein Rad54 promotes non-crossover recombination between centromere repeats to prevent isochromosome formation...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27694623/esc2-promotes-mus81-complex-activity-via-its-sumo-like-and-dna-binding-domains
#18
Marek Sebesta, Madhusoodanan Urulangodi, Barbora Stefanovie, Barnabas Szakal, Martin Pacesa, Michael Lisby, Dana Branzei, Lumir Krejci
Replication across damaged DNA templates is accompanied by transient formation of sister chromatid junctions (SCJs). Cells lacking Esc2, an adaptor protein containing no known enzymatic domains, are defective in the metabolism of these SCJs. However, how Esc2 is involved in the metabolism of SCJs remains elusive. Here we show interaction between Esc2 and a structure-specific endonuclease Mus81-Mms4 (the Mus81 complex), their involvement in the metabolism of SCJs, and the effects Esc2 has on the enzymatic activity of the Mus81 complex...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27672038/nucleolytic-processing-of-aberrant-replication-intermediates-by-an-exo1-dna2-sae2-axis-counteracts-fork-collapse-driven-chromosome-instability
#19
Arianna Colosio, Camilla Frattini, Grazia Pellicanò, Sara Villa-Hernández, Rodrigo Bermejo
Problems during DNA replication underlie genomic instability and drive malignant transformation. The DNA damage checkpoint stabilizes stalled replication forks thus counteracting aberrant fork transitions, DNA breaks and chromosomal rearrangements. We analyzed fork processing in checkpoint deficient cells by coupling psoralen crosslinking with replication intermediate two-dimensional gel analysis. This revealed a novel role for Exo1 nuclease in resecting reversed replication fork structures and counteracting the accumulation of aberrant intermediates resembling fork cleavage products...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27649880/roles-of-eukaryotic-topoisomerases-in-transcription-replication-and-genomic-stability
#20
REVIEW
Yves Pommier, Yilun Sun, Shar-Yin N Huang, John L Nitiss
Topoisomerases introduce transient DNA breaks to relax supercoiled DNA, remove catenanes and enable chromosome segregation. Human cells encode six topoisomerases (TOP1, TOP1mt, TOP2α, TOP2β, TOP3α and TOP3β), which act on a broad range of DNA and RNA substrates at the nuclear and mitochondrial genomes. Their catalytic intermediates, the topoisomerase cleavage complexes (TOPcc), are therapeutic targets of various anticancer drugs. TOPcc can also form on damaged DNA during replication and transcription, and engage specific repair pathways, such as those mediated by tyrosyl-DNA phosphodiesterase 1 (TDP1) and TDP2 and by endonucleases (MRE11, XPF-ERCC1 and MUS81)...
November 2016: Nature Reviews. Molecular Cell Biology
keyword
keyword
70919
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"