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
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
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 |
| ||
GA13-26629S, projekt VaV |
|