Condensin extrudes DNA loops in steps up to hundreds of base pairs that are generated by ATP binding events.
Nucleic Acids Res
; 50(2): 820-832, 2022 01 25.
Article
em En
| MEDLINE
| ID: mdl-34951453
ABSTRACT
The condensin SMC protein complex organizes chromosomal structure by extruding loops of DNA. Its ATP-dependent motor mechanism remains unclear but likely involves steps associated with large conformational changes within the â¼50 nm protein complex. Here, using high-resolution magnetic tweezers, we resolve single steps in the loop extrusion process by individual yeast condensins. The measured median step sizes range between 20-40 nm at forces of 1.0-0.2 pN, respectively, comparable with the holocomplex size. These large steps show that, strikingly, condensin typically reels in DNA in very sizeable amounts with â¼200 bp on average per single extrusion step at low force, and occasionally even much larger, exceeding 500 bp per step. Using Molecular Dynamics simulations, we demonstrate that this is due to the structural flexibility of the DNA polymer at these low forces. Using ATP-binding-impaired and ATP-hydrolysis-deficient mutants, we find that ATP binding is the primary step-generating stage underlying DNA loop extrusion. We discuss our findings in terms of a scrunching model where a stepwise DNA loop extrusion is generated by an ATP-binding-induced engagement of the hinge and the globular domain of the SMC complex.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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DNA Fúngico
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Cromatina
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Adenosina Trifosfatases
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Proteínas de Saccharomyces cerevisiae
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Complexos Multiproteicos
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Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2022
Tipo de documento:
Article