A structure-function analysis of the yeast Elg1 protein reveals
the importance of PCNA unloading in genome stability
maintenance

J 2017

A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance

SHEMESH, Keren, Marek ŠEBESTA, Martin PAČESA, Soumitra SAU, Alex BRONSTEIN et. al.

Základní údaje

Originální název

A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance

Autoři

SHEMESH, Keren (376 Izrael), Marek ŠEBESTA (703 Slovensko, domácí), Martin PAČESA (703 Slovensko, domácí), Soumitra SAU (376 Izrael), Alex BRONSTEIN (376 Izrael), Oren PARNAS (376 Izrael), Batia LIEFSHITZ (376 Izrael), Česlovas VENCLOVAS (440 Litva), Lumír KREJČÍ (203 Česká republika, garant, domácí) a Martin KUPIEC (376 Izrael)

Vydání

Nucleic Acids Research, Oxford, Oxford University Press, 2017, 0305-1048

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 11.561

Kód RIV

RIV/00216224:14110/17:00094734

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1093/nar/gkw1348

UT WoS

000398376200030

Klíčová slova anglicky

REPLICATION FACTOR-C; SISTER-CHROMATID COHESION; ALTERNATIVE RFC COMPLEX; DNA-POLYMERASE DELTA; CELL NUCLEAR ANTIGEN; SUMO-MODIFIED PCNA; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; REPAIR SYNTHESIS; CLAMP LOADERS

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 20. 3. 2018 16:01, Soňa Böhmová

Anotace

V originále

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 rad5 Delta mutants to DNA damage by allowing translesion 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.

Návaznosti

GAP207/12/2323, projekt VaV

Název: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I

Investor: Grantová agentura ČR, Endonuleázová a translokázová aktivita v restrikčních-modifikačních komplexech typu I

GA13-26629S, projekt VaV

Název: SUMO a stability genomu

Investor: Grantová agentura ČR, SUMO a stability genomu

Citovat

SHEMESH, Keren, Marek ŠEBESTA, Martin PAČESA, Soumitra SAU, Alex BRONSTEIN, Oren PARNAS, Batia LIEFSHITZ, Česlovas VENCLOVAS, Lumír KREJČÍ a 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: Oxford University Press, 2017, roč. 45, č. 6, s. 3189-3203. ISSN 0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkw1348.

@article{1379549,
   author = {Shemesh, Keren and Šebesta, Marek and Pačesa, Martin and Sau, Soumitra and Bronstein, Alex and Parnas, Oren and Liefshitz, Batia and Venclovas, Česlovas and Krejčí, Lumír and Kupiec, Martin},
   article_location = {Oxford},
   article_number = {6},
   doi = {http://dx.doi.org/10.1093/nar/gkw1348},
   keywords = {REPLICATION FACTOR-C; SISTER-CHROMATID COHESION; ALTERNATIVE RFC COMPLEX; DNA-POLYMERASE DELTA; CELL NUCLEAR ANTIGEN; SUMO-MODIFIED PCNA; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; REPAIR SYNTHESIS; CLAMP LOADERS},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance},
   volume = {45},
   year = {2017}
}

TY  - JOUR
ID  - 1379549
AU  - Shemesh, Keren - Šebesta, Marek - Pačesa, Martin - Sau, Soumitra - Bronstein, Alex - Parnas, Oren - Liefshitz, Batia - Venclovas, Česlovas - Krejčí, Lumír - Kupiec, Martin
PY  - 2017
TI  - A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance
JF  - Nucleic Acids Research
VL  - 45
IS  - 6
SP  - 3189-3203
EP  - 3189-3203
PB  - Oxford University Press
SN  - 03051048
KW  - REPLICATION FACTOR-C
KW  - SISTER-CHROMATID COHESION
KW  - ALTERNATIVE RFC COMPLEX
KW  - DNA-POLYMERASE DELTA
KW  - CELL NUCLEAR ANTIGEN
KW  - SUMO-MODIFIED PCNA
KW  - SACCHAROMYCES-CEREVISIAE
KW  - ESCHERICHIA-COLI
KW  - REPAIR SYNTHESIS
KW  - CLAMP LOADERS
N2  - 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 rad5 Delta mutants to DNA damage by allowing translesion 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.
ER  -

SHEMESH, Keren, Marek ŠEBESTA, Martin PAČESA, Soumitra SAU, Alex BRONSTEIN, Oren PARNAS, Batia LIEFSHITZ, Česlovas VENCLOVAS, Lumír KREJČÍ a Martin KUPIEC. A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2017, roč.~45, č.~6, s.~3189-3203. ISSN~0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkw1348.

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