keyword
https://read.qxmd.com/read/35333860/sumo-mediated-recruitment-allows-timely-function-of-the-yen1-nuclease-in-mitotic-cells
#1
JOURNAL ARTICLE
Hugo Dorison, Ibtissam Talhaoui, Gerard Mazón
The post-translational modification of DNA damage response proteins with SUMO is an important mechanism to orchestrate a timely and orderly recruitment of repair factors to damage sites. After DNA replication stress and double-strand break formation, a number of repair factors are SUMOylated and interact with other SUMOylated factors, including the Yen1 nuclease. Yen1 plays a critical role in ensuring genome stability and unperturbed chromosome segregation by removing covalently linked DNA intermediates between sister chromatids that are formed by homologous recombination...
March 2022: PLoS Genetics
https://read.qxmd.com/read/35013185/mechanism-for-inverted-repeat-recombination-induced-by-a-replication-fork-barrier
#2
JOURNAL ARTICLE
Léa Marie, Lorraine S Symington
Replication stress and abundant repetitive sequences have emerged as primary conditions underlying genomic instability in eukaryotes. To gain insight into the mechanism of recombination between repeated sequences in the context of replication stress, we used a prokaryotic Tus/Ter barrier designed to induce transient replication fork stalling near inverted repeats in the budding yeast genome. Our study reveals that the replication fork block stimulates a unique recombination pathway dependent on Rad51 strand invasion and Rad52-Rad59 strand annealing activities, Mph1/Rad5 fork remodelers, Mre11/Exo1/Dna2 resection machineries, Rad1-Rad10 nuclease and DNA polymerase δ...
January 10, 2022: Nature Communications
https://read.qxmd.com/read/34928393/canonical-and-novel-non-canonical-activities-of-the-holliday-junction-resolvase-yen1
#3
JOURNAL ARTICLE
Raquel Carreira, F Javier Aguado, Vanesa Hurtado-Nieves, Miguel G Blanco
Yen1 and GEN1 are members of the Rad2/XPG family of nucleases that were identified as the first canonical nuclear Holliday junction (HJ) resolvases in budding yeast and humans due to their ability to introduce two symmetric, coordinated incisions on opposite strands of the HJ, yielding nicked DNA products that could be readily ligated. While GEN1 has been extensively characterized in vitro, much less is known about the biochemistry of Yen1. Here, we have performed the first in-depth characterization of purified Yen1...
December 20, 2021: Nucleic Acids Research
https://read.qxmd.com/read/34575966/the-cdc14-phosphatase-controls-resolution-of-recombination-intermediates-and-crossover-formation-during-meiosis
#4
JOURNAL ARTICLE
Paula Alonso-Ramos, David Álvarez-Melo, Katerina Strouhalova, Carolina Pascual-Silva, George B Garside, Meret Arter, Teresa Bermejo, Rokas Grigaitis, Rahel Wettstein, Marta Fernández-Díaz, Joao Matos, Marco Geymonat, Pedro A San-Segundo, Jesús A Carballo
Meiotic defects derived from incorrect DNA repair during gametogenesis can lead to mutations, aneuploidies and infertility. The coordinated resolution of meiotic recombination intermediates is required for crossover formation, ultimately necessary for the accurate completion of both rounds of chromosome segregation. Numerous master kinases orchestrate the correct assembly and activity of the repair machinery. Although much less is known, the reversal of phosphorylation events in meiosis must also be key to coordinate the timing and functionality of repair enzymes...
September 10, 2021: International Journal of Molecular Sciences
https://read.qxmd.com/read/33322845/implications-of-metastable-nicks-and-nicked-holliday-junctions-in-processing-joint-molecules-in-mitosis-and-meiosis
#5
JOURNAL ARTICLE
Félix Machín
Joint molecules (JMs) are intermediates of homologous recombination (HR). JMs rejoin sister or homolog chromosomes and must be removed timely to allow segregation in anaphase. Current models pinpoint Holliday junctions (HJs) as a central JM. The canonical HJ (cHJ) is a four-way DNA that needs specialized nucleases, a.k.a. resolvases, to resolve into two DNA molecules. Alternatively, a helicase-topoisomerase complex can deal with pairs of cHJs in the dissolution pathway. Aside from cHJs, HJs with a nick at the junction (nicked HJ; nHJ) can be found in vivo and are extremely good substrates for resolvases in vitro...
December 12, 2020: Genes
https://read.qxmd.com/read/32840779/holliday-junction-resolution
#6
JOURNAL ARTICLE
Raquel Carreira, F Javier Aguado, Tomas Lama-Diaz, Miguel G Blanco
Holliday junctions are four-way DNA structures that may arise during meiotic recombination, double-strand break repair, or postreplicative repair by the reciprocal exchange of single strands between two DNA molecules. Given their ability to effectively bridge two sister chromatids or homologous chromosomes, cells have implemented various pathways to ensure their timely removal. One of them is the nucleolytic processing of the Holliday junctions by specialized structure-selective endonucleases termed resolvases, which sever the connection between the linked molecules...
2021: Methods in Molecular Biology
https://read.qxmd.com/read/32762846/mechanisms-underlying-genome-instability-mediated-by-formation-of-foldback-inversions-in-saccharomyces-cerevisiae
#7
JOURNAL ARTICLE
Bin-Zhong Li, Christopher D Putnam, Richard David Kolodner
Foldback inversions, also called inverted duplications, have been observed in human genetic diseases and cancers. Here, we used a Saccharomyces cerevisiae genetic system that generates gross chromosomal rearrangements (GCRs) mediated by foldback inversions combined with whole-genome sequencing to study their formation. Foldback inversions were mediated by formation of single-stranded DNA hairpins. Two types of hairpins were identified: small-loop hairpins that were suppressed by MRE11 , SAE2 , SLX1 , and YKU80 and large-loop hairpins that were suppressed by YEN1 , TEL1 , SWR1 , and MRC1 ...
August 7, 2020: ELife
https://read.qxmd.com/read/32388488/size-dependent-antirecombinogenic-effect-of-short-spacers-on-palindrome-recombinogenicity
#8
JOURNAL ARTICLE
Marina Svetec Miklenić, Nikolina Gatalica, Angela Matanović, Bojan Žunar, Anamarija Štafa, Berislav Lisnić, Ivan Krešimir Svetec
Palindromic sequences in DNA can instigate genetic recombination and genome instability, which can result in devastating conditions such as the Emmanuel syndrome. Palindrome recombinogenicity increases with its size and sequence similarity between palindrome arms, while quasipalindromes with long spacers are less recombinogenic. However, the minimal spacer length, which could reduce or abolish palindrome recombinogenicity in the eukaryotic genome, was never determined. Therefore, we constructed a series of palindromes containing spacers of lengths ranging from 0 (perfect palindrome) to 10 bp and tested their recombinogenicity in yeast Saccharomyces cerevisiae...
June 2020: DNA Repair
https://read.qxmd.com/read/32352375/an-advanced-cell-cycle-tag-toolbox-reveals-principles-underlying-temporal-control-of-structure-selective-nucleases
#9
JOURNAL ARTICLE
Julia Bittmann, Rokas Grigaitis, Lorenzo Galanti, Silas Amarell, Florian Wilfling, Joao Matos, Boris Pfander
Cell cycle tags allow to restrict target protein expression to specific cell cycle phases. Here, we present an advanced toolbox of cell cycle tag constructs in budding yeast with defined and compatible peak expression that allow comparison of protein functionality at different cell cycle phases. We apply this technology to the question of how and when Mus81-Mms4 and Yen1 nucleases act on DNA replication or recombination structures. Restriction of Mus81-Mms4 to M phase but not S phase allows a wildtype response to various forms of replication perturbation and DNA damage in S phase, suggesting it acts as a post-replicative resolvase...
April 30, 2020: ELife
https://read.qxmd.com/read/31214148/phosphorylation-of-the-archaeal-holliday-junction-resolvase-hjc-inhibits-its-catalytic-activity-and-facilitates-dna-repair-in-sulfolobus-islandicus-rey15a
#10
JOURNAL ARTICLE
Qihong Huang, Joseph Badys Mayaka, Qing Zhong, Chao Zhang, Guihua Hou, Jinfeng Ni, Yulong Shen
Protein phosphorylation is one of the main protein post-translational modifications and regulates DNA repair in eukaryotes. Archaeal genomes encode eukaryotic-like DNA repair proteins and protein kinases (ePKs), and several proteins involved in homologous recombination repair (HRR) including Hjc, a conserved Holliday junction (HJ) resolvase in Archaea, undergo phosphorylation, indicating that phosphorylation plays important roles in HRR. Herein, we performed phosphorylation analysis of Hjc by various ePKs from Sulfolobus islandicus ...
2019: Frontiers in Microbiology
https://read.qxmd.com/read/31018130/sequence-and-nuclease-requirements-for-breakage-and-healing-of-a-structure-forming-at-n-sequence-within-fragile-site-fra16d
#11
JOURNAL ARTICLE
Simran Kaushal, Charles E Wollmuth, Kohal Das, Suzanne E Hile, Samantha B Regan, Ryan P Barnes, Alice Haouzi, Soo Mi Lee, Nealia C M House, Michael Guyumdzhyan, Kristin A Eckert, Catherine H Freudenreich
Common fragile sites (CFSs) are genomic regions that display gaps and breaks in human metaphase chromosomes under replication stress and are often deleted in cancer cells. We studied an ∼300-bp subregion (Flex1) of human CFS FRA16D in yeast and found that it recapitulates characteristics of CFS fragility in human cells. Flex1 fragility is dependent on the ability of a variable-length AT repeat to form a cruciform structure that stalls replication. Fragility at Flex1 is initiated by structure-specific endonuclease Mus81-Mms4 acting together with the Slx1-4/Rad1-10 complex, whereas Yen1 protects Flex1 against breakage...
April 23, 2019: Cell Reports
https://read.qxmd.com/read/30897139/helicase-sumo-targeted-ubiquitin-ligase-uls1-interacts-with-the-holliday-junction-resolvase-yen1
#12
JOURNAL ARTICLE
Stefanie L Bauer, Jiang Chen, Stefan U Åström
Resolution of branched DNA structures is pivotal for repair of stalled replication forks and meiotic recombination intermediates. The Yen1 nuclease cleaves both Holliday junctions and replication forks. We show that Yen1 interacts physically with Uls1, a suggested SUMO-targeted ubiquitin ligase that also contains a SWI/SNF-family ATPase-domain. Yen1 is SUMO-modified in its noncatalytic carboxyl terminus and DNA damage induces SUMOylation. SUMO-modification of Yen1 strengthens the interaction to Uls1, and mutations in SUMO interaction motifs in Uls1 weakens the interaction...
2019: PloS One
https://read.qxmd.com/read/30479332/slx5-slx8-ubiquitin-ligase-targets-active-pools-of-the-yen1-nuclease-to-limit-crossover-formation
#13
JOURNAL ARTICLE
Ibtissam Talhaoui, Manuel Bernal, Janet R Mullen, Hugo Dorison, Benoit Palancade, Steven J Brill, Gerard Mazón
The repair of double-stranded DNA breaks (DSBs) by homologous recombination involves the formation of branched intermediates that can lead to crossovers following nucleolytic resolution. The nucleases Mus81-Mms4 and Yen1 are tightly controlled during the cell cycle to limit the extent of crossover formation and preserve genome integrity. Here we show that Yen1 is further regulated by sumoylation and ubiquitination. In vivo, Yen1 becomes sumoylated under conditions of DNA damage by the redundant activities of Siz1 and Siz2 SUMO ligases...
November 27, 2018: Nature Communications
https://read.qxmd.com/read/30453647/fanconi-anaemia-like-mph1-helicase-backs-up-rad54-and-rad5-to-circumvent-replication-stress-driven-chromosome-bridges
#14
JOURNAL ARTICLE
Jonay García-Luis, Félix Machín
Homologous recombination (HR) is a preferred mechanism to deal with DNA replication impairments. However, HR synapsis gives rise to joint molecules (JMs) between the nascent sister chromatids, challenging chromosome segregation in anaphase. Joint molecules are resolved by the actions of several structure-selective endonucleases (SSEs), helicases and topoisomerases. Previously, we showed that yeast double mutants for the Mus81-Mms4 and Yen1 SSEs lead to anaphase bridges (ABs) after replication stress. Here, we have studied the role of the Mph1 helicase in preventing these anaphase aberrations...
November 17, 2018: Genes
https://read.qxmd.com/read/29920281/regulated-crossing-over-requires-inactivation-of-yen1-gen1-resolvase-during-meiotic-prophase-i
#15
JOURNAL ARTICLE
Meret Arter, Vanesa Hurtado-Nieves, Ashwini Oke, Tangna Zhuge, Rahel Wettstein, Jennifer C Fung, Miguel G Blanco, Joao Matos
During meiosis, crossover recombination promotes the establishment of physical connections between homologous chromosomes, enabling their bipolar segregation. To ensure that persistent recombination intermediates are disengaged prior to the completion of meiosis, the Yen1(GEN1) resolvase is strictly activated at the onset of anaphase II. Whether controlled activation of Yen1 is important for meiotic crossing-over is unknown. Here, we show that CDK-mediated phosphorylation of Yen1 averts its pervasive recruitment to recombination intermediates during prophase I...
June 18, 2018: Developmental Cell
https://read.qxmd.com/read/29176630/break-induced-replication-promotes-formation-of-lethal-joint-molecules-dissolved-by-srs2
#16
JOURNAL ARTICLE
Rajula Elango, Ziwei Sheng, Jessica Jackson, Jenna DeCata, Younis Ibrahim, Nhung T Pham, Diana H Liang, Cynthia J Sakofsky, Alessandro Vindigni, Kirill S Lobachev, Grzegorz Ira, Anna Malkova
Break-induced replication (BIR) is a DNA double-strand break repair pathway that leads to genomic instabilities similar to those observed in cancer. BIR proceeds by a migrating bubble where asynchrony between leading and lagging strand synthesis leads to accumulation of long single-stranded DNA (ssDNA). It remains unknown how this ssDNA is prevented from unscheduled pairing with the template, which can lead to genomic instability. Here, we propose that uncontrolled Rad51 binding to this ssDNA promotes formation of toxic joint molecules that are counteracted by Srs2...
November 27, 2017: Nature Communications
https://read.qxmd.com/read/28781165/multi-invasions-are-recombination-byproducts-that-induce-chromosomal-rearrangements
#17
JOURNAL ARTICLE
Aurèle Piazza, William Douglass Wright, Wolf-Dietrich Heyer
Inaccurate repair of broken chromosomes generates structural variants that can fuel evolution and inflict pathology. We describe a novel rearrangement mechanism in which translocation between intact chromosomes is induced by a lesion on a third chromosome. This multi-invasion-induced rearrangement (MIR) stems from a homologous recombination byproduct, where a broken DNA end simultaneously invades two intact donors. No homology is required between the donors, and the intervening sequence from the invading molecule is inserted at the translocation site...
August 10, 2017: Cell
https://read.qxmd.com/read/28512214/correction-for-mu%C3%A3-oz-galv%C3%A3-n-et-al-distinct-roles-of-mus81-yen1-slx1-slx4-and-rad1-nucleases-in-the-repair-of-replication-born-double-strand-breaks-by-sister-chromatid-exchange
#18
JOURNAL ARTICLE
Sandra Muñoz-Galván, Cristina Tous, Miguel G Blanco, Erin K Schwartz, Kirk T Ehmsen, Stephen C West, Wolf-Dietrich Heyer, Andrés Aguilera
No abstract text is available yet for this article.
June 1, 2017: Molecular and Cellular Biology
https://read.qxmd.com/read/28369583/substrate-preference-of-gen-endonucleases-highlights-the-importance-of-branched-structures-as-dna-damage-repair-intermediates
#19
JOURNAL ARTICLE
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...
May 19, 2017: Nucleic Acids Research
https://read.qxmd.com/read/28357386/a-new-role-for-holliday-junction-resolvase-yen1-in-processing-dna-replication-intermediates-exposes-dna2-as-an-accessory-replicative-helicase
#20
COMMENT
Benoît Falquet, Ulrich Rass
DNA replication is mediated by a multi-protein complex known as the replisome. With the hexameric MCM (minichromosome maintenance) replicative helicase at its core, the replisome splits the parental DNA strands, forming replication forks (RFs), where it catalyses coupled leading and lagging strand DNA synthesis. While replication is a highly effective process, intrinsic and oncogene-induced replication stress impedes the progression of replisomes along chromosomes. As a consequence, RFs stall, arrest, and collapse, jeopardizing genome stability...
January 2, 2017: Microbial Cell
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