scholarly journals Smc5/6 Is Required for Repair at Collapsed Replication Forks

2006 ◽  
Vol 26 (24) ◽  
pp. 9387-9401 ◽  
Author(s):  
Eleni Ampatzidou ◽  
Anja Irmisch ◽  
Matthew J. O'Connell ◽  
Johanne M. Murray
Keyword(s):  
Homologous Recombination ◽  
Protein Complexes ◽  
S Phase ◽  
Replication Forks ◽  
Replication Arrest ◽  
Recombination Proteins ◽  
Independent Functions ◽  
Chromatid Cohesion ◽  
Recombination Repair ◽  
Structural Maintenance Of Chromosome

ABSTRACT In eukaryotes, three pairs of structural-maintenance-of-chromosome (SMC) proteins are found in conserved multisubunit protein complexes required for chromosomal organization. Cohesin, the Smc1/3 complex, mediates sister chromatid cohesion while two condensin complexes containing Smc2/4 facilitate chromosome condensation. Smc5/6 scaffolds an essential complex required for homologous recombination repair. We have examined the response of smc6 mutants to the inhibition of DNA replication. We define homologous recombination-dependent and -independent functions for Smc6 during replication inhibition and provide evidence for a Rad60-independent function within S phase, in addition to a Rad60-dependent function following S phase. Both genetic and physical data show that when forks collapse (i.e., are not stabilized by the Cds1Chk2 checkpoint), Smc6 is required for the effective repair of resulting lesions but not for the recruitment of recombination proteins. We further demonstrate that when the Rad60-dependent, post-S-phase Smc6 function is compromised, the resulting recombination-dependent DNA intermediates that accumulate following release from replication arrest are not recognized by the G2/M checkpoint.

scholarly journals Rings, bracelet or snaps: fashionable alternatives for Smc complexes

2005 ◽  
Vol 360 (1455) ◽  
pp. 537-542 ◽  
Author(s):  
Catherine E Huang ◽  
Mark Milutinovich ◽  
Douglas Koshland
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Protein Complexes ◽  
Coiled Coil ◽  
Structural Features ◽  
Gene Repression ◽  
Chromosome Organization ◽  
Structural Components ◽  
Chromatid Cohesion ◽  
Structural Maintenance Of Chromosome

The mechanism of higher order chromosome organization has eluded researchers for over 100 years. A breakthrough occurred with the discovery of multi-subunit protein complexes that contain a core of two molecules from the structural maintenance of chromosome (Smc) family. Smc complexes are important structural components of chromosome organization in diverse aspects of DNA metabolism, including sister chromatid cohesion, condensation, global gene repression, DNA repair and homologous recombination. In these different processes, Smc complexes may facilitate chromosome organization by tethering together two parts of the same or different chromatin strands. The mechanism of tethering by Smc complexes remains to be elucidated, but a number of intriguing topological alternatives are suggested by the unusual structural features of Smc complexes, including their large coiled-coil domains and ATPase activities. Distinguishing between these possibilities will require innovative new approaches.

scholarly journals Spatiotemporal dynamics of homologous recombination repair at single collapsed replication forks

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Donna R. Whelan ◽  
Wei Ting C. Lee ◽  
Yandong Yin ◽  
Dylan M. Ofri ◽  
Keria Bermudez-Hernandez ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Spatiotemporal Dynamics ◽  
Homologous Recombination Repair ◽  
Replication Forks ◽  
Recombination Repair

scholarly journals Moonlighting at replication forks - a new life for homologous recombination proteins BRCA1, BRCA2 and RAD51

FEBS Letters ◽  
2017 ◽  
Vol 591 (8) ◽  
pp. 1083-1100 ◽  
Author(s):  
Arun Mouli Kolinjivadi ◽  
Vincenzo Sannino ◽  
Anna de Antoni ◽  
Hervé Técher ◽  
Giorgio Baldi ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Replication Forks ◽  
Recombination Proteins ◽  
Brca1 Brca2

scholarly journals Shu Proteins Promote the Formation of Homologous Recombination Intermediates That Are Processed by Sgs1-Rmi1-Top3

2007 ◽  
Vol 18 (10) ◽  
pp. 4062-4073 ◽  
Author(s):  
Hocine W. Mankouri ◽  
Hien-Ping Ngo ◽  
Ian D. Hickson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Homologous Recombination ◽  
S Phase ◽  
Specific Role ◽  
Homologous Recombination Repair ◽  
Recombination Repair ◽  
Mutant Phenotypes ◽  
Precise Role

CSM2, PSY3, SHU1, and SHU2 (collectively referred to as the SHU genes) were identified in Saccharomyces cerevisiae as four genes in the same epistasis group that suppress various sgs1 and top3 mutant phenotypes when mutated. Although the SHU genes have been implicated in homologous recombination repair (HRR), their precise role(s) within this pathway remains poorly understood. Here, we have identified a specific role for the Shu proteins in a Rad51/Rad54-dependent HRR pathway(s) to repair MMS-induced lesions during S-phase. We show that, although mutation of RAD51 or RAD54 prevented the formation of MMS-induced HRR intermediates (X-molecules) arising during replication in sgs1 cells, mutation of SHU genes attenuated the level of these structures. Similar findings were also observed in shu1 cells in which Rmi1 or Top3 function was impaired. We propose a model in which the Shu proteins act in HRR to promote the formation of HRR intermediates that are processed by the Sgs1-Rmi1-Top3 complex.

scholarly journals Hit the brakes – a new perspective on the loop extrusion mechanism of cohesin and other SMC complexes

2021 ◽  
Vol 134 (1) ◽  
pp. jcs247577
Author(s):  
Avi Matityahu ◽  
Itay Onn
Keyword(s):  
Present Model ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Order Structure ◽  
Chromatid Cohesion ◽  
Topologically Associated Domains ◽  
Extrusion Mechanism ◽  
New Perspective ◽  
Structural Maintenance Of Chromosome

ABSTRACTThe three-dimensional structure of chromatin is determined by the action of protein complexes of the structural maintenance of chromosome (SMC) family. Eukaryotic cells contain three SMC complexes, cohesin, condensin, and a complex of Smc5 and Smc6. Initially, cohesin was linked to sister chromatid cohesion, the process that ensures the fidelity of chromosome segregation in mitosis. In recent years, a second function in the organization of interphase chromatin into topologically associated domains has been determined, and loop extrusion has emerged as the leading mechanism of this process. Interestingly, fundamental mechanistic differences exist between mitotic tethering and loop extrusion. As distinct molecular switches that aim to suppress loop extrusion in different biological contexts have been identified, we hypothesize here that loop extrusion is the default biochemical activity of cohesin and that its suppression shifts cohesin into a tethering mode. With this model, we aim to provide an explanation for how loop extrusion and tethering can coexist in a single cohesin complex and also apply it to the other eukaryotic SMC complexes, describing both similarities and differences between them. Finally, we present model-derived molecular predictions that can be tested experimentally, thus offering a new perspective on the mechanisms by which SMC complexes shape the higher-order structure of chromatin.

scholarly journals EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair

PLoS Genetics ◽  
2015 ◽  
Vol 11 (12) ◽  
pp. e1005675 ◽  
Author(s):  
Yuehan Wu ◽  
Suk-Hee Lee ◽  
Elizabeth A. Williamson ◽  
Brian L. Reinert ◽  
Ju Hwan Cho ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Genome Stability ◽  
Homologous Recombination Repair ◽  
Replication Forks ◽  
Recombination Repair ◽  
End Resection

scholarly journals Replication dynamics of recombination-dependent replication forks

2020 ◽  
Author(s):  
Karel Naiman ◽  
Eduard Campillo-Funollet ◽  
Adam T. Watson ◽  
Alice Budden ◽  
Izumi Miyabe ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Homologous Recombination ◽  
Replication Fork ◽  
S Phase ◽  
Replication Forks ◽  
Leading Strand ◽  
The Stability ◽  
Lagging Strand

AbstractDNA replication fidelity is essential for maintaining genetic stability. Forks arrested at replication fork barriers can be stabilised by the intra-S phase checkpoint, subsequently being rescued by a converging fork, or resuming when the barrier is removed. However, some arrested forks cannot be stabilised and fork convergence cannot rescue in all situations. Thus, cells have developed homologous recombination-dependent mechanisms to restart persistently inactive forks. To understand HR-restart we use polymerase usage sequencing to visualize in vivo replication dynamics at an S. pombe replication barrier, RTS1, and model replication by Monte Carlo simulation. We show that HR-restarted forks synthesise both strands with Pol δ for up to 30 kb without maturing to a δ/ε configuration and that Pol α is not used significantly on either strand, suggesting the lagging strand template remains as a gap that is filled in by Pol δ later. We further demonstrate that HR-restarted forks progress uninterrupted through a fork barrier that arrests canonical forks. Finally, by manipulating lagging strand resection during HR-restart by deleting pku70, we show that the leading strand initiates replication at the same position, signifying the stability of the 3’ single strand in the context of increased resection.

scholarly journals Esc2 and Sgs1 Act in Functionally Distinct Branches of the Homologous Recombination Repair Pathway inSaccharomyces cerevisiae

2009 ◽  
Vol 20 (6) ◽  
pp. 1683-1694 ◽  
Author(s):  
Hocine W. Mankouri ◽  
Hien-Ping Ngo ◽  
Ian D. Hickson
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Structural Similarity ◽  
S Phase ◽  
Homologous Recombination Repair ◽  
Dna Damage Checkpoint ◽  
Checkpoint Signaling ◽  
Checkpoint Response ◽  
Recombination Repair ◽  
Anemia Group

Esc2 is a member of the RENi family of SUMO-like domain proteins and is implicated in gene silencing in Saccharomyces cerevisiae. Here, we identify a dual role for Esc2 during S-phase in mediating both intra-S-phase DNA damage checkpoint signaling and preventing the accumulation of Rad51-dependent homologous recombination repair (HRR) intermediates. These roles are qualitatively similar to those of Sgs1, the yeast ortholog of the human Bloom's syndrome protein, BLM. However, whereas mutation of either ESC2 or SGS1 leads to the accumulation of unprocessed HRR intermediates in the presence of MMS, the accumulation of these structures in esc2 (but not sgs1) mutants is entirely dependent on Mph1, a protein that shows structural similarity to the Fanconi anemia group M protein (FANCM). In the absence of both Esc2 and Sgs1, the intra-S-phase DNA damage checkpoint response is compromised after exposure to MMS, and sgs1esc2 cells attempt to undergo mitosis with unprocessed HRR intermediates. We propose a model whereby Esc2 acts in an Mph1-dependent process, separately from Sgs1, to influence the repair/tolerance of MMS-induced lesions during S-phase.

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