Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

K. Shemesh, M. Sebesta, M. Pacesa, S. Sau, A. Bronstein, O. Parnas, B. Liefshitz, C. Venclovas, L. Krejci, M. Kupiec,

. 2017 ; 45 (6) : 3189-3203.

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc17031115

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc17031115
003      
CZ-PrNML
005      
20171025115427.0
007      
ta
008      
171025s2017 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/nar/gkw1348 $2 doi
035    __
$a (PubMed)28108661
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Shemesh, Keren $u Department of Molecular Microbiology and Biotechnology, Ramat Aviv 69978, Israel.
245    12
$a A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance / $c K. Shemesh, M. Sebesta, M. Pacesa, S. Sau, A. Bronstein, O. Parnas, B. Liefshitz, C. Venclovas, L. Krejci, M. Kupiec,
520    9_
$a 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.
650    _2
$a transportní proteiny $x chemie $x genetika $x metabolismus $7 D002352
650    _2
$a chromatin $x metabolismus $7 D002843
650    _2
$a DNA $x biosyntéza $7 D004247
650    12
$a poškození DNA $7 D004249
650    _2
$a DNA-helikasy $x genetika $7 D004265
650    12
$a nestabilita genomu $7 D042822
650    _2
$a methylmethansulfonát $x toxicita $7 D008741
650    _2
$a mutace $7 D009154
650    _2
$a proliferační antigen buněčného jádra $x metabolismus $7 D018809
650    _2
$a rekombinace genetická $7 D011995
650    _2
$a Saccharomyces cerevisiae - proteiny $x chemie $x genetika $x metabolismus $7 D029701
650    _2
$a strukturní homologie proteinů $7 D040681
650    _2
$a vztahy mezi strukturou a aktivitou $7 D013329
650    _2
$a suprese genetická $7 D013489
655    _2
$a časopisecké články $7 D016428
700    1_
$a Sebesta, Marek $u Department of Biology, Masaryk University, CZ-625 00 Brno, Czech Republic.
700    1_
$a Pacesa, Martin $u Department of Biology, Masaryk University, CZ-625 00 Brno, Czech Republic.
700    1_
$a Sau, Soumitra $u Department of Molecular Microbiology and Biotechnology, Ramat Aviv 69978, Israel.
700    1_
$a Bronstein, Alex $u Department of Molecular Microbiology and Biotechnology, Ramat Aviv 69978, Israel.
700    1_
$a Parnas, Oren $u Department of Molecular Microbiology and Biotechnology, Ramat Aviv 69978, Israel.
700    1_
$a Liefshitz, Batia $u Department of Molecular Microbiology and Biotechnology, Ramat Aviv 69978, Israel.
700    1_
$a Venclovas, Ceslovas $u Institute of Biotechnology, Vilnius University, Graiciuno 8, Vilnius LT-02241, Lithuania.
700    1_
$a Krejci, Lumir $u Department of Biology, Masaryk University, CZ-625 00 Brno, Czech Republic. National Center for Biomolecular Research, Masaryk University, CZ-625 00 Brno, Czech Republic. International Clinical Research Center, St. Anne's University Hospital in Brno, CZ- 656 91 Brno, Czech Republic.
700    1_
$a Kupiec, Martin $u Department of Molecular Microbiology and Biotechnology, Ramat Aviv 69978, Israel.
773    0_
$w MED00003554 $t Nucleic acids research $x 1362-4962 $g Roč. 45, č. 6 (2017), s. 3189-3203
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28108661 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20171025 $b ABA008
991    __
$a 20171025115509 $b ABA008
999    __
$a ok $b bmc $g 1254708 $s 992142
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 45 $c 6 $d 3189-3203 $i 1362-4962 $m Nucleic acids research $n Nucleic Acids Res $x MED00003554
LZP    __
$a Pubmed-20171025

Find record

Citation metrics

Archiving options