What AlphaFold tells us about cohesin’s retention on and release from chromosomes DOI Open Access
Kim Nasmyth, Byung‐Gil Lee, Maurici B. Roig

et al.

Published: Oct. 23, 2023

Cohesin is a trimeric complex containing pair of SMC proteins (Smc1 and Smc3) whose ATPase domains at the end long coiled coils (CC) are interconnected by Scc1. During interphase, it organizes chromosomal DNA topology extruding loops in manner dependent on Scc1’s association with two large hook shaped called SA (yeast: Scc3) Nipbl (Scc2). The latter’s replacement Pds5 recruits Wapl, which induces release from chromatin via process requiring dissociation N-terminal domain (NTD) Smc3. If blocked Esco (Eco)-mediated Smc3 acetylation, cohesin merely maintains pre-existing loops, but third fate occurs during replication, when Pds5-containing associates Sororin forms structures that hold sister DNAs together. How Wapl blocks has hitherto remained mysterious. In twenty years since their discovery, not single testable hypothesis been proposed as to role. Here, AlphaFold 2 (AF) three-dimensional protein structure predictions lead us propose formation quarternary between SA, Pds5, NTD, latter juxtaposed (and subsequently sequestered by) highly conserved cleft within Wapl’s C-terminal (CTD). AF also reveals how arises distortion Smc3’s CC induced engagement domains, acetyl transferases recruited prevents binding Smc3/Scc1 interface. Our hypotheses explain phenotypes numerous existing mutations testable.

Language: Английский

The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity DOI

Vidhya Krishnamoorthy,

Martina Foglizzo, Robert L. Dilley

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2250 - 2268.e31

Published: March 29, 2024

Language: Английский

Citations

3
Cohesin chromatin loop formation by an extrinsic motor DOI Creative Commons
Thomas M Guérin, Christopher Barrington, Georgii Pobegalov

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 30, 2023

Abstract The ring-shaped cohesin complex topologically entraps two DNAs to establish sister chromatid cohesion 1–3 . Cohesin also shapes the interphase chromatin landscape with wide-ranging implications for gene regulation 4–7 , which is thought achieve by actively extruding DNA loops without entrapping 8–11 ‘loop extrusion’ hypothesis finds motivation from in vitro observations 12–14 – whether this process underlies vivo loop formation remains untested. Here, using budding yeast S. cerevisiae we generate variants that have lost their ability extrude but retain entrap DNA. Analysis of these suggests form independently extrusion. Instead, find transcription promotes formation, as well acts an extrinsic motor expands and defines ultimate positions. Our results necessitate a re-evaluation extrusion model point alternative mechanism cohesin-dependent organisation. We propose cohesin, akin establishment at replication forks, forms DNA-DNA capture places transcription, thus unifying cohesin’s roles chromosome segregation genome

Language: Английский

Citations

7
Control of DNA replication in vitro using a reversible replication barrier DOI

Emma J. Vontalge,

Tamar Kavlashvili,

Steven N Dahmen

et al.

Nature Protocols, Journal Year: 2024, Volume and Issue: 19(7), P. 1940 - 1983

Published: April 9, 2024

Language: Английский

Citations

2
Replisome passage through the cohesin ring DOI Creative Commons
Samson Glaser, Maxim I. Molodtsov, John F.X. Diffley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Following eukaryotic genome replication, the two newly synthesised sister chromatids remain paired by ring-shaped cohesin complex, enabling their faithful segregation to daughter cells during cell divisions 1 . Cohesin topologically embraces DNA already before replication 2–5 , and replisome passage through ring is thought of as a fail-safe mechanism ensuring that entraps both products 6,7 Whether replisomes indeed pass rings remains unknown. Here, we use biochemical reconstitution 4,8,9 single molecule fluorescence microscopy directly visualise replisome-cohesin encounters. We find translocating replicative Cdc45-Mcm2-7-GINS (CMG) helicase frequently an obstacle cohesin, but likelihood with which CMG passes increases in presence components known chromatid cohesion functions 7,10–14 or preventing from freely sliding along template DNA. retains topological entrapment passage, suggesting ring. The frequency further when fully reconstituted encounter rings, resulting successful establishment between products. Our findings demonstrate existence simple links chromosome segregation, rings.

Language: Английский

Citations

2
Replisome-cohesin interactions provided by the Tof1-Csm3 and Mrc1 cohesion establishment factors DOI Creative Commons

Sudikchya Shrestha,

Masashi Minamino, Zhuo A. Chen

et al.

Chromosoma, Journal Year: 2023, Volume and Issue: 132(2), P. 117 - 135

Published: May 11, 2023

Abstract The chromosomal cohesin complex establishes sister chromatid cohesion during S phase, which forms the basis for faithful segregation of DNA replication products cell divisions. Cohesion establishment is defective in absence either three non-essential Saccharomyces cerevisiae fork components Tof1-Csm3 and Mrc1. Here, we investigate how these conserved factors contribute to establishment. Mrc1 serve known roles replication, including checkpoint signaling, securing speed, as well recruiting topoisomerase I histone chaperone FACT. By modulating each functions independently, rule out that one explains contribution Instead, using purified components, reveal direct multipronged protein interactions with complex. Our findings open possibility a series physical between facilitate successful replication.

Language: Английский

Citations

4
Chromatin organization in myelodysplastic syndrome DOI
Jane Jialu Xu, Aaron D. Viny

Experimental Hematology, Journal Year: 2024, Volume and Issue: 134, P. 104216 - 104216

Published: April 4, 2024

Language: Английский

Citations

1
What AlphaFold tells us about cohesin’s retention on and release from chromosomes DOI Open Access
Kim Nasmyth, Byung‐Gil Lee, Maurici B. Roig

et al.

Published: June 15, 2023

Abstract Cohesin is a trimeric complex containing pair of SMC proteins (Smc1 and Smc3) whose ATPase domains at the end long coiled coils (CC) are interconnected by Scc1. During interphase, it organizes chromosomal DNA topology extruding loops in manner dependent on Scc1’s association with two large hook shaped called SA (yeast: Scc3) Nipbl (Scc2). The latter’s replacement Pds5 recruits Wapl, which induces release from chromatin via process requiring dissociation N-terminal domain (NTD) Smc3. If blocked Esco (Eco)-mediated Smc3 acetylation, cohesin merely maintains pre-existing loops, but third fate occurs during replication, when Pds5-containing associates Sororin forms structures that hold sister DNAs together. How Wapl blocks has hitherto remained mysterious. In twenty years since their discovery, not single testable hypothesis been proposed as to role. Here, AlphaFold 2 (AF) three-dimensional protein structure predictions lead us propose formation quarternary between SA, Pds5, NTD, latter juxtaposed (and subsequently sequestered by) highly conserved cleft within Wapl’s C-terminal (CTD). AF also reveals how arises distortion Smc3’s CC induced engagement domains, acetyl transferases recruited prevents binding Smc3/Scc1 interface. Our hypotheses explain phenotypes numerous existing mutations testable.

Language: Английский

Citations

2
Chromatin assembly factor-1 preserves genome stability in ctf4∆ cells by promoting sister chromatid cohesion DOI Creative Commons
Nagham Ghaddar, Pierre Luciano, Vincent Géli

et al.

Cell Stress, Journal Year: 2023, Volume and Issue: 7(9), P. 69 - 89

Published: Aug. 18, 2023

Chromatin assembly and the establishment of sister chromatid cohesion are intimately connected to progression DNA replication forks. Here we examined genetic interaction between heterotrimeric chromatin factor-1 (CAF-1), a central component during replication, core replisome Ctf4. We find that CAF-1 deficient cells as well affected in newly-synthesized H3-H4 histones deposition exhibit severe negative growth with ctf4Δ mutant. dissected role maintenance genome stability yeast cells. In absence CTF4, is essential for viability experiencing problems, lacking functional S-phase checkpoint or spindle checkpoint, repair pathways involving homologous recombination. present evidence affects cohesin association DNA-damage-dependent manner maintain CTF4. also show Eco1-catalyzed Smc3 acetylation reduced CAF-1. Furthermore, describe interactions genes involved loading, stabilization, indicating crucial when affected. Finally, our data indicate CAF-1-dependent pathway required functionally distinct from Rtt101-Mms1-Mms22 which functions replicated assembly. Collectively, results suggest by creates environment favors maintains integrity.

Language: Английский

Citations

2
What AlphaFold tells us about cohesin’s retention on and release from chromosomes DOI Open Access
Kim Nasmyth, Byung‐Gil Lee, Maurici B. Roig

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 14, 2023

ABSTRACT Cohesin is a trimeric complex containing pair of SMC proteins (Smc1 and Smc3) whose ATPase domains at the end long coiled coils (CC) are interconnected by Scc1. During interphase, it organizes chromosomal DNA topology extruding loops in manner dependent on Scc1’s association with two large hook shaped called SA (yeast: Scc3) Nipbl (Scc2). The latter’s replacement Pds5 recruits Wapl, which induces release from chromatin via process requiring dissociation N-terminal domain (NTD) Smc3. If blocked Esco (Eco)-mediated Smc3 acetylation, cohesin merely maintains pre-existing loops, but third fate occurs during replication, when Pds5-containing associates Sororin forms structures that hold sister DNAs together. How Wapl blocks has hitherto remained mysterious. In twenty years since their discovery, not single testable hypothesis been proposed as to role. Here, AlphaFold 2 (AF) three-dimensional protein structure predictions lead us propose formation quarternary between SA, Pds5, NTD, latter juxtaposed (and subsequently sequestered by) highly conserved cleft within Wapl’s C-terminal (CTD). AF also reveals how arises distortion Smc3’s CC induced engagement domains, acetyl transferases recruited prevents binding Smc3/Scc1 interface. Our hypotheses explain phenotypes numerous existing mutations testable.

Language: Английский

Citations

1
Cell biology: Converging paths to cohesion DOI
Roel Oldenkamp, Benjamin D. Rowland

Current Biology, Journal Year: 2024, Volume and Issue: 34(14), P. R680 - R682

Published: July 1, 2024

Language: Английский

Citations

0