RESUMO
Cohesin entraps sister DNAs within tripartite rings created by pairwise interactions between Smc1, Smc3, and Scc1. Because Smc1/3 ATPase heads can also interact with each other, cohesin rings have the potential to form a variety of sub-compartments. Using in vivo cysteine cross-linking, we show that when Smc1 and Smc3 ATPases are engaged in the presence of ATP (E heads), cohesin rings generate a "SMC (S) compartment" between hinge and E heads and a "kleisin (K) compartment" between E heads and their associated kleisin subunit. Upon ATP hydrolysis, cohesin's heads associate in a different mode, in which their signature motifs and their coiled coils are closely juxtaposed (J heads), creating alternative S and K compartments. We show that K compartments of either E or J type can entrap single DNAs, that acetylation of Smc3 during S phase is associated with J heads, and that sister DNAs are entrapped in J-K compartments.
Assuntos
Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/genética , DNA/genética , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Trifosfato de Adenosina/química , Trifosfato de Adenosina/genética , Cromátides/genética , DNA/química , Dimerização , Modelos Moleculares , Estrutura Terciária de Proteína , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Troca de Cromátide Irmã/genética , CoesinasRESUMO
All animals have evolved the ability to survive nutrient deprivation, and nutrient signaling pathways are conserved modulators of health and disease. In C. elegans, late-larval starvation provokes the adult reproductive diapause (ARD), a long-lived quiescent state that enables survival for months without food, yet underlying molecular mechanisms remain unknown. Here, we show that ARD is distinct from other forms of diapause, showing little requirement for canonical longevity pathways, autophagy, and fat metabolism. Instead it requires the HLH-30/TFEB transcription factor to promote the morphological and physiological remodeling involved in ARD entry, survival, and recovery, suggesting that HLH-30 is a master regulator of reproductive quiescence. HLH-30 transcriptome and genetic analyses reveal that Max-like HLH factors, AMP-kinase, mTOR, protein synthesis, and mitochondrial fusion are target processes that promote ARD longevity. ARD thus rewires metabolism to ensure long-term survival and may illuminate similar mechanisms acting in stem cell quiescence and long-term fasting.