Does the mechanism of #NonsenseMediatedDecay (#NMD) differ between yeast & animals? @GrailleLab &co use the structure of Upf1 RNA #helicase in complex with Nmd4 to show that metazoan SMG6 NMD factor binds to Upf1 using a conserved binding mode #PLOSBiology https://plos.io/4eEZgtL
Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans

The mechanism of nonsense-mediated mRNA decay (NMD) is thought to differ between yeast and metazoa, even though the Upf1 RNA helicase is universally conserved. This study uses the crystal structure of Upf1 in complex with Nmd4 to show that the metazoan SMG6 NMD factor binds to Upf1 using an evolutionarily conserved binding mode.

CMG #helicase disassembly is essential and driven by two pathways in budding yeast
Karim Labib and colleagues show that Pif1-family helicases mediate an ancestral pathway for ‘old’ #replisome disassembly during the subsequent S-phase
https://www.embopress.org/doi/full/10.1038/s44318-024-00161-x
Convo over at the X-birdie about how one can increase the throughput of @nanopore #nanopore sequencing by shielding from light
https://twitter.com/SurroundScience/status/1705643180123914702?t=9RPiXwlebta8blBr6Ev1Iw&s=19
This is nuts and the differential increase (more for shorter than longer sequences) makes for some interesting head scratching and free association thinking.
Could all this be due to the #helicase activity?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516474/
https://pubs.acs.org/doi/10.1021/jacs.3c05254
#sequencing
Mrinalini Watsa on X

So @nanopore discovered something a few days ago - and it has to do with light. And they posted this image (sorry, too good not to share off the community). Yes, that’s 469% increased output. So, we decided to give it a shot and …

X (formerly Twitter)

#Microcephaly protein #DONSON is a novel factor needed for CMG #helicase assembly during vertebrate DNA #replication initiation

Yoshitami Hashimoto and colleagues

https://www.embopress.org/doi/10.15252/embj.2023114131

Basic fundamental research on how DNA functions and how our cells work on a molecular level is critical to broader insights and innovations.

Delft University of Technology scientists have more precisely found how the helicase CMG unwinds DNA during replication and its full functionality in doing so with a new mechanism.

#Science #DNA #Replication #Helicase #CMG #Biology #Biochemistry #Molecular #SciComm

https://www.nature.com/articles/s41467-023-37093-9

Nucleotide binding halts diffusion of the eukaryotic replicative helicase during activation - Nature Communications

Here the authors examine fully reconstituted and activated CMG helicases at the single-molecule level. They observe unidirectional translocation by CMG in ATP and diffusive motion by CMG without ATP, where the latter can be halted by nucleotide binding.

Nature

What is the #molecular basis of #syntheticlethality between loss of Werner #helicase #WRN and #mismatchrepair #MMR proteins particularly in #cancer cells with #microsatellite instability?

Using #biochemcial assays, Petr Cejka and colleages, Bellinzona LRB, show how they synergistically and independently unfold #cruciform #DNA structures, with WRN preventing their cleavage by #SLX1-#SLX4 structure-specific #endonuclease and DNA breakage

https://www.embopress.org/doi/10.15252/embj.2022111998