Detailed Information on Publication Record
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.Basic information
Original name
A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance
Authors
SHEMESH, Keren (376 Israel), Marek ŠEBESTA (703 Slovakia, belonging to the institution), Martin PAČESA (703 Slovakia, belonging to the institution), Soumitra SAU (376 Israel), Alex BRONSTEIN (376 Israel), Oren PARNAS (376 Israel), Batia LIEFSHITZ (376 Israel), Česlovas VENCLOVAS (440 Lithuania), Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution) and Martin KUPIEC (376 Israel)
Edition
Nucleic Acids Research, Oxford, Oxford University Press, 2017, 0305-1048
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
10608 Biochemistry and molecular biology
Country of publisher
United Kingdom of Great Britain and Northern Ireland
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 11.561
RIV identification code
RIV/00216224:14110/17:00094734
Organization unit
Faculty of Medicine
UT WoS
000398376200030
Keywords in English
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
Tags
International impact, Reviewed
Změněno: 20/3/2018 16:01, Soňa Böhmová
Abstract
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.
Links
GAP207/12/2323, research and development project |
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GA13-26629S, research and development project |
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