Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Science ; 376(6597): 1087-1094, 2022 06 03.
Article in English | MEDLINE | ID: mdl-35653469

ABSTRACT

Structural maintenance of chromosomes (SMC) protein complexes structure genomes by extruding DNA loops, but the molecular mechanism that underlies their activity has remained unknown. We show that the active condensin complex entraps the bases of a DNA loop transiently in two separate chambers. Single-molecule imaging and cryo-electron microscopy suggest a putative power-stroke movement at the first chamber that feeds DNA into the SMC-kleisin ring upon adenosine triphosphate binding, whereas the second chamber holds on upstream of the same DNA double helix. Unlocking the strict separation of "motor" and "anchor" chambers turns condensin from a one-sided into a bidirectional DNA loop extruder. We conclude that the orientation of two topologically bound DNA segments during the SMC reaction cycle determines the directionality of DNA loop extrusion.


Subject(s)
Adenosine Triphosphatases , DNA-Binding Proteins , DNA , Multiprotein Complexes , Adenosine Triphosphatases/chemistry , Cryoelectron Microscopy , DNA/chemistry , DNA-Binding Proteins/chemistry , Multiprotein Complexes/chemistry , Nucleic Acid Conformation , Single Molecule Imaging
2.
Curr Opin Struct Biol ; 65: 102-109, 2020 12.
Article in English | MEDLINE | ID: mdl-32674008

ABSTRACT

Structural Maintenance of Chromosomes (SMC) protein complexes play key roles in the three-dimensional organization of genomes in all kingdoms of life. Recent insights from chromosome contact mapping experiments and single-molecule imaging assays suggest that these complexes achieve distinct cellular functions by extruding large loops of DNA while they move along the chromatin fiber. In this short review, we summarize recent insights into the molecular architecture of these unconventional DNA motor complexes, their interaction with their DNA substrates, and the remarkable dynamic changes they can undergo during their ATPase reaction cycle.


Subject(s)
Chromosomes , DNA-Binding Proteins , DNA , Multiprotein Complexes , Bacteria , Chromosomes/chemistry , Chromosomes/metabolism , DNA/chemistry , DNA/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , Multiprotein Complexes/chemistry , Multiprotein Complexes/metabolism , Protein Binding , Yeasts
3.
EMBO J ; 37(1): 89-101, 2018 01 04.
Article in English | MEDLINE | ID: mdl-28947618

ABSTRACT

The expression of intron-containing genes in eukaryotes requires generation of protein-coding messenger RNAs (mRNAs) via RNA splicing, whereby the spliceosome removes non-coding introns from pre-mRNAs and joins exons. Spliceosomes must ensure accurate removal of highly diverse introns. We show that Sde2 is a ubiquitin-fold-containing splicing regulator that supports splicing of selected pre-mRNAs in an intron-specific manner in Schizosaccharomyces pombe Both fission yeast and human Sde2 are translated as inactive precursor proteins harbouring the ubiquitin-fold domain linked through an invariant GGKGG motif to a C-terminal domain (referred to as Sde2-C). Precursor processing after the first di-glycine motif by the ubiquitin-specific proteases Ubp5 and Ubp15 generates a short-lived activated Sde2-C fragment with an N-terminal lysine residue, which subsequently gets incorporated into spliceosomes. Absence of Sde2 or defects in Sde2 activation both result in inefficient excision of selected introns from a subset of pre-mRNAs. Sde2 facilitates spliceosomal association of Cactin/Cay1, with a functional link between Sde2 and Cactin further supported by genetic interactions and pre-mRNA splicing assays. These findings suggest that ubiquitin-like processing of Sde2 into a short-lived activated form may function as a checkpoint to ensure proper splicing of certain pre-mRNAs in fission yeast.


Subject(s)
DNA-Binding Proteins/metabolism , Introns , RNA Splicing , Schizosaccharomyces pombe Proteins/metabolism , Schizosaccharomyces/genetics , Ubiquitin/metabolism , DNA-Binding Proteins/genetics , Genomic Instability , Humans , RNA Precursors/genetics , RNA, Fungal/genetics , RNA, Fungal/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Schizosaccharomyces/metabolism , Schizosaccharomyces pombe Proteins/genetics , Spliceosomes
SELECTION OF CITATIONS
SEARCH DETAIL
...