CRISPR/Cas9 genome-wide screens using sterol-sensitive endogenous HMG-CoA reductase (HMGCR) reporter identify the sterol-responsive RNF145 and gp78 as independently responsible for sterol-accelerated degradation of HMGCR, the rate-limiting enzyme of cholesterol biosynthesis.
The CMG complex, the replicative helicase in eukaryotes, uses a different mechanism from bacterial and viral helicases by engaging both strands of parental DNA with substantial force and unwinding the duplex within the central channel of CMG.
Biochemical data demonstrate an unexpected and critical function for the enigmatic Mcm10 protein in helping the eukaryotic CMG helicase/replisome bypass roadblocks on the DNA that may also explain Mcm10 function at origins of replication.
The inhibition of sterol-accelerated degradation of HMG CoA reductase by the vitamin K2 synthetic enzyme UBIAD1 may contribute to the accumulation of cholesterol that is associated with Schnyder corneal dystrophy.
In Escherichia coli structural maintenance of chromosomes (SMC) complex, MukBEF, a dimeric MukF kleisin binds and activates MukB SMC ATPases through two independent interfaces provided by distinct MukF N- and C-terminal domains.
In invertebrate and vertebrate models of Spinal Muscular Atrophy, diminished SMN protein causes Gemin3-dependent decreases in microRNA function, leading to upregulated M2 muscarinic receptor and deleterious consequences.