---
_id: '8449'
abstract:
- lang: eng
text: Ensuring the correct folding of RNA molecules in the cell is of major importance
for a large variety of biological functions. Therefore, chaperone proteins that
assist RNA in adopting their functionally active states are abundant in all living
organisms. An important feature of RNA chaperone proteins is that they do not
require an external energy source to perform their activity, and that they interact
transiently and non-specifically with their RNA targets. So far, little is known
about the mechanistic details of the RNA chaperone activity of these proteins.
Prominent examples of RNA chaperones are bacterial cold shock proteins (Csp) that
have been reported to bind single-stranded RNA and DNA. Here, we have used advanced
NMR spectroscopy techniques to investigate at atomic resolution the RNA-melting
activity of CspA, the major cold shock protein of Escherichia coli, upon binding
to different RNA hairpins. Real-time NMR provides detailed information on the
folding kinetics and folding pathways. Finally, comparison of wild-type CspA with
single-point mutants and small peptides yields insights into the complementary
roles of aromatic and positively charged amino-acid side chains for the RNA chaperone
activity of the protein.
article_processing_charge: No
article_type: original
author:
- first_name: Enrico
full_name: Rennella, Enrico
last_name: Rennella
- first_name: Tomáš
full_name: Sára, Tomáš
last_name: Sára
- first_name: Michael
full_name: Juen, Michael
last_name: Juen
- first_name: Christoph
full_name: Wunderlich, Christoph
last_name: Wunderlich
- first_name: Lionel
full_name: Imbert, Lionel
last_name: Imbert
- first_name: Zsofia
full_name: Solyom, Zsofia
last_name: Solyom
- first_name: Adrien
full_name: Favier, Adrien
last_name: Favier
- first_name: Isabel
full_name: Ayala, Isabel
last_name: Ayala
- first_name: Katharina
full_name: Weinhäupl, Katharina
last_name: Weinhäupl
- first_name: Paul
full_name: Schanda, Paul
id: 7B541462-FAF6-11E9-A490-E8DFE5697425
last_name: Schanda
orcid: 0000-0002-9350-7606
- first_name: Robert
full_name: Konrat, Robert
last_name: Konrat
- first_name: Christoph
full_name: Kreutz, Christoph
last_name: Kreutz
- first_name: Bernhard
full_name: Brutscher, Bernhard
last_name: Brutscher
citation:
ama: Rennella E, Sára T, Juen M, et al. RNA binding and chaperone activity of the
E.coli cold-shock protein CspA. Nucleic Acids Research. 2017;45(7):4255-4268.
doi:10.1093/nar/gkx044
apa: Rennella, E., Sára, T., Juen, M., Wunderlich, C., Imbert, L., Solyom, Z., …
Brutscher, B. (2017). RNA binding and chaperone activity of the E.coli cold-shock
protein CspA. Nucleic Acids Research. Oxford University Press. https://doi.org/10.1093/nar/gkx044
chicago: Rennella, Enrico, Tomáš Sára, Michael Juen, Christoph Wunderlich, Lionel
Imbert, Zsofia Solyom, Adrien Favier, et al. “RNA Binding and Chaperone Activity
of the E.Coli Cold-Shock Protein CspA.” Nucleic Acids Research. Oxford
University Press, 2017. https://doi.org/10.1093/nar/gkx044.
ieee: E. Rennella et al., “RNA binding and chaperone activity of the E.coli
cold-shock protein CspA,” Nucleic Acids Research, vol. 45, no. 7. Oxford
University Press, pp. 4255–4268, 2017.
ista: Rennella E, Sára T, Juen M, Wunderlich C, Imbert L, Solyom Z, Favier A, Ayala
I, Weinhäupl K, Schanda P, Konrat R, Kreutz C, Brutscher B. 2017. RNA binding
and chaperone activity of the E.coli cold-shock protein CspA. Nucleic Acids Research.
45(7), 4255–4268.
mla: Rennella, Enrico, et al. “RNA Binding and Chaperone Activity of the E.Coli
Cold-Shock Protein CspA.” Nucleic Acids Research, vol. 45, no. 7, Oxford
University Press, 2017, pp. 4255–68, doi:10.1093/nar/gkx044.
short: E. Rennella, T. Sára, M. Juen, C. Wunderlich, L. Imbert, Z. Solyom, A. Favier,
I. Ayala, K. Weinhäupl, P. Schanda, R. Konrat, C. Kreutz, B. Brutscher, Nucleic
Acids Research 45 (2017) 4255–4268.
date_created: 2020-09-18T10:06:34Z
date_published: 2017-04-20T00:00:00Z
date_updated: 2021-01-12T08:19:20Z
day: '20'
doi: 10.1093/nar/gkx044
extern: '1'
fulldoi: https://doi.org/10.1093/nar/gkx044
intvolume: ' 45'
issue: '7'
language:
- iso: eng
month: '04'
oa_version: None
page: 4255-4268
publication: Nucleic Acids Research
publication_identifier:
issn:
- 0305-1048
- 1362-4962
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
status: public
title: RNA binding and chaperone activity of the E.coli cold-shock protein CspA
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 45
year: '2017'
...
---
DOAJ_listed: '1'
_id: '18372'
abstract:
- lang: eng
text: The sliding clamp, PCNA, plays a central role in DNA replication and repair.
In the moving replication fork, PCNA is present at the leading strand and at each
of the Okazaki fragments that are formed on the lagging strand. PCNA enhances
the processivity of the replicative polymerases and provides a landing platform
for other proteins and enzymes. The loading of the clamp onto DNA is performed
by the Replication Factor C (RFC) complex, whereas its unloading can be carried
out by an RFC-like complex containing Elg1. Mutations in ELG1 lead to DNA damage
sensitivity and genome instability. To characterize the role of Elg1 in maintaining
genomic integrity, we used homology modeling to generate a number of site-specific
mutations in ELG1 that exhibit different PCNA unloading capabilities. We show
that the sensitivity to DNA damaging agents and hyper-recombination of these alleles
correlate with their ability to unload PCNA from the chromatin. Our results indicate
that retention of modified and unmodified PCNA on the chromatin causes genomic
instability. We also show, using purified proteins, that the Elg1 complex inhibits
DNA synthesis by unloading SUMOylated PCNA from the DNA. Additionally, we find
that mutations in ELG1 suppress the sensitivity of rad5Δ mutants to DNA damage
by allowing trans-lesion synthesis to take place. Taken together, the data indicate
that the Elg1–RLC complex plays an important role in the maintenance of genomic
stability by unloading PCNA from the chromatin.
article_processing_charge: No
author:
- first_name: Keren
full_name: Shemesh, Keren
last_name: Shemesh
- first_name: Marek
full_name: Sebesta, Marek
last_name: Sebesta
- first_name: Martin
full_name: Pacesa, Martin
last_name: Pacesa
- first_name: Soumitra
full_name: Sau, Soumitra
last_name: Sau
- first_name: Alexander
full_name: Bronstein, Alexander
id: 58f3726e-7cba-11ef-ad8b-e6e8cb3904e6
last_name: Bronstein
orcid: 0000-0001-9699-8730
- first_name: Oren
full_name: Parnas, Oren
last_name: Parnas
- first_name: Batia
full_name: Liefshitz, Batia
last_name: Liefshitz
- first_name: Česlovas
full_name: Venclovas, Česlovas
last_name: Venclovas
- first_name: Lumir
full_name: Krejci, Lumir
last_name: Krejci
- first_name: Martin
full_name: Kupiec, Martin
last_name: Kupiec
citation:
ama: Shemesh K, Sebesta M, Pacesa M, et al. A structure-function analysis of the
yeast Elg1 protein reveals the importance of PCNA unloading in genome stability
maintenance. Nucleic Acids Research. 2017;45(6):3189-3203. doi:10.1093/nar/gkw1348
apa: Shemesh, K., Sebesta, M., Pacesa, M., Sau, S., Bronstein, A. M., Parnas, O.,
… Kupiec, M. (2017). A structure-function analysis of the yeast Elg1 protein reveals
the importance of PCNA unloading in genome stability maintenance. Nucleic Acids
Research. Oxford University Press (OUP). https://doi.org/10.1093/nar/gkw1348
chicago: Shemesh, Keren, Marek Sebesta, Martin Pacesa, Soumitra Sau, Alex M. Bronstein,
Oren Parnas, Batia Liefshitz, Česlovas Venclovas, Lumir Krejci, and Martin Kupiec.
“A Structure-Function Analysis of the Yeast Elg1 Protein Reveals the Importance
of PCNA Unloading in Genome Stability Maintenance.” Nucleic Acids Research.
Oxford University Press (OUP), 2017. https://doi.org/10.1093/nar/gkw1348.
ieee: K. Shemesh et al., “A structure-function analysis of the yeast Elg1
protein reveals the importance of PCNA unloading in genome stability maintenance,”
Nucleic Acids Research, vol. 45, no. 6. Oxford University Press (OUP),
pp. 3189–3203, 2017.
ista: Shemesh K, Sebesta M, Pacesa M, Sau S, Bronstein AM, Parnas O, Liefshitz B,
Venclovas Č, Krejci L, Kupiec M. 2017. A structure-function analysis of the yeast
Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance.
Nucleic Acids Research. 45(6), 3189–3203.
mla: Shemesh, Keren, et al. “A Structure-Function Analysis of the Yeast Elg1 Protein
Reveals the Importance of PCNA Unloading in Genome Stability Maintenance.” Nucleic
Acids Research, vol. 45, no. 6, Oxford University Press (OUP), 2017, pp. 3189–203,
doi:10.1093/nar/gkw1348.
short: K. Shemesh, M. Sebesta, M. Pacesa, S. Sau, A.M. Bronstein, O. Parnas, B.
Liefshitz, Č. Venclovas, L. Krejci, M. Kupiec, Nucleic Acids Research 45 (2017)
3189–3203.
date_created: 2024-10-15T11:20:54Z
date_published: 2017-04-07T00:00:00Z
date_updated: 2024-12-18T12:31:56Z
day: '07'
doi: 10.1093/nar/gkw1348
extern: '1'
fulldoi: https://doi.org/10.1093/nar/gkw1348
intvolume: ' 45'
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1093/nar/gkw1348
month: '04'
oa: 1
oa_version: Published Version
page: 3189 - 3203
publication: Nucleic Acids Research
publication_identifier:
issn:
- 0305-1048
- 1362-4962
publication_status: published
publisher: Oxford University Press (OUP)
quality_controlled: '1'
scopus_import: '1'
status: public
title: A structure-function analysis of the yeast Elg1 protein reveals the importance
of PCNA unloading in genome stability maintenance
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 45
year: '2017'
...
---
_id: '9017'
abstract:
- lang: eng
text: MCM2 is a subunit of the replicative helicase machinery shown to interact
with histones H3 and H4 during the replication process through its N-terminal
domain. During replication, this interaction has been proposed to assist disassembly
and assembly of nucleosomes on DNA. However, how this interaction participates
in crosstalk with histone chaperones at the replication fork remains to be elucidated.
Here, we solved the crystal structure of the ternary complex between the histone-binding
domain of Mcm2 and the histones H3-H4 at 2.9 Å resolution. Histones H3 and H4
assemble as a tetramer in the crystal structure, but MCM2 interacts only with
a single molecule of H3-H4. The latter interaction exploits binding surfaces that
contact either DNA or H2B when H3-H4 dimers are incorporated in the nucleosome
core particle. Upon binding of the ternary complex with the histone chaperone
ASF1, the histone tetramer dissociates and both MCM2 and ASF1 interact simultaneously
with the histones forming a 1:1:1:1 heteromeric complex. Thermodynamic analysis
of the quaternary complex together with structural modeling support that ASF1
and MCM2 could form a chaperoning module for histones H3 and H4 protecting them
from promiscuous interactions. This suggests an additional function for MCM2 outside
its helicase function as a proper histone chaperone connected to the replication
pathway.
article_processing_charge: No
article_type: original
author:
- first_name: Nicolas
full_name: Richet, Nicolas
last_name: Richet
- first_name: Danni
full_name: Liu, Danni
last_name: Liu
- first_name: Pierre
full_name: Legrand, Pierre
last_name: Legrand
- first_name: Christophe
full_name: Velours, Christophe
last_name: Velours
- first_name: Armelle
full_name: Corpet, Armelle
last_name: Corpet
- first_name: Albane
full_name: Gaubert, Albane
last_name: Gaubert
- first_name: May M
full_name: Bakail, May M
id: FB3C3F8E-522F-11EA-B186-22963DDC885E
last_name: Bakail
orcid: 0000-0002-9592-1587
- first_name: Gwenaelle
full_name: Moal-Raisin, Gwenaelle
last_name: Moal-Raisin
- first_name: Raphael
full_name: Guerois, Raphael
last_name: Guerois
- first_name: Christel
full_name: Compper, Christel
last_name: Compper
- first_name: Arthur
full_name: Besle, Arthur
last_name: Besle
- first_name: Berengère
full_name: Guichard, Berengère
last_name: Guichard
- first_name: Genevieve
full_name: Almouzni, Genevieve
last_name: Almouzni
- first_name: Françoise
full_name: Ochsenbein, Françoise
last_name: Ochsenbein
citation:
ama: Richet N, Liu D, Legrand P, et al. Structural insight into how the human helicase
subunit MCM2 may act as a histone chaperone together with ASF1 at the replication
fork. Nucleic Acids Research. 2015;43(3):1905-1917. doi:10.1093/nar/gkv021
apa: Richet, N., Liu, D., Legrand, P., Velours, C., Corpet, A., Gaubert, A., … Ochsenbein,
F. (2015). Structural insight into how the human helicase subunit MCM2 may act
as a histone chaperone together with ASF1 at the replication fork. Nucleic
Acids Research. Oxford University Press. https://doi.org/10.1093/nar/gkv021
chicago: Richet, Nicolas, Danni Liu, Pierre Legrand, Christophe Velours, Armelle
Corpet, Albane Gaubert, May M Bakail, et al. “Structural Insight into How the
Human Helicase Subunit MCM2 May Act as a Histone Chaperone Together with ASF1
at the Replication Fork.” Nucleic Acids Research. Oxford University Press,
2015. https://doi.org/10.1093/nar/gkv021.
ieee: N. Richet et al., “Structural insight into how the human helicase subunit
MCM2 may act as a histone chaperone together with ASF1 at the replication fork,”
Nucleic Acids Research, vol. 43, no. 3. Oxford University Press, pp. 1905–1917,
2015.
ista: Richet N, Liu D, Legrand P, Velours C, Corpet A, Gaubert A, Bakail MM, Moal-Raisin
G, Guerois R, Compper C, Besle A, Guichard B, Almouzni G, Ochsenbein F. 2015.
Structural insight into how the human helicase subunit MCM2 may act as a histone
chaperone together with ASF1 at the replication fork. Nucleic Acids Research.
43(3), 1905–1917.
mla: Richet, Nicolas, et al. “Structural Insight into How the Human Helicase Subunit
MCM2 May Act as a Histone Chaperone Together with ASF1 at the Replication Fork.”
Nucleic Acids Research, vol. 43, no. 3, Oxford University Press, 2015,
pp. 1905–17, doi:10.1093/nar/gkv021.
short: N. Richet, D. Liu, P. Legrand, C. Velours, A. Corpet, A. Gaubert, M.M. Bakail,
G. Moal-Raisin, R. Guerois, C. Compper, A. Besle, B. Guichard, G. Almouzni, F.
Ochsenbein, Nucleic Acids Research 43 (2015) 1905–1917.
date_created: 2021-01-19T11:01:01Z
date_published: 2015-02-18T00:00:00Z
date_updated: 2023-02-23T13:46:50Z
day: '18'
doi: 10.1093/nar/gkv021
extern: '1'
external_id:
pmid:
- '25618846'
fulldoi: https://doi.org/10.1093/nar/gkv021
intvolume: ' 43'
issue: '3'
language:
- iso: eng
month: '02'
oa_version: Published Version
page: 1905-1917
pmid: 1
publication: Nucleic Acids Research
publication_identifier:
issn:
- 1362-4962
- 0305-1048
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
status: public
title: Structural insight into how the human helicase subunit MCM2 may act as a histone
chaperone together with ASF1 at the replication fork
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 43
year: '2015'
...