DNA damage tolerance, mismatch repair and genome instability

BioEssays ◽  
1994 ◽  
Vol 16 (11) ◽  
pp. 833-839 ◽  
Author(s):  
P. Karran ◽  
M. Bignami
Keyword(s):  
Dna Damage ◽  
Mismatch Repair ◽  
Damage Tolerance ◽  
Genome Instability ◽  
Dna Damage Tolerance

scholarly journals Helicase-Like Transcription Factor HLTF and E3 Ubiquitin Ligase SHPRH Confer DNA Damage Tolerance through Direct Interactions with Proliferating Cell Nuclear Antigen (PCNA)

2020 ◽  
Vol 21 (3) ◽  
pp. 693 ◽  
Author(s):  
Mareike Seelinger ◽  
Marit Otterlei
Keyword(s):  
Dna Damage ◽  
Transcription Factor ◽  
Damage Tolerance ◽  
Genome Instability ◽  
Ring Finger ◽  
Nuclear Antigen ◽  
Common Mutation ◽  
Dna Damage Tolerance ◽  
Replicative Stress ◽  
Template Switch

To prevent replication fork collapse and genome instability under replicative stress, DNA damage tolerance (DDT) mechanisms have evolved. The RAD5 homologs, HLTF (helicase-like transcription factor) and SHPRH (SNF2, histone-linker, PHD and RING finger domain-containing helicase), both ubiquitin ligases, are involved in several DDT mechanisms; DNA translesion synthesis (TLS), fork reversal/remodeling and template switch (TS). Here we show that these two human RAD5 homologs contain functional APIM PCNA interacting motifs. Our results show that both the role of HLTF in TLS in HLTF overexpressing cells, and nuclear localization of SHPRH, are dependent on interaction of HLTF and SHPRH with PCNA. Additionally, we detected multiple changes in the mutation spectra when APIM in overexpressed HLTF or SHPRH were mutated compared to overexpressed wild type proteins. In plasmids from cells overexpressing the APIM mutant version of HLTF, we observed a decrease in C to T transitions, the most common mutation caused by UV irradiation, and an increase in mutations on the transcribed strand. These results strongly suggest that direct binding of HLTF and SHPRH to PCNA is vital for their function in DDT.

scholarly journals Functional and Physical Interaction of Yeast Mgs1 with PCNA: Impact on RAD6-Dependent DNA Damage Tolerance

2006 ◽  
Vol 26 (14) ◽  
pp. 5509-5517 ◽  
Author(s):  
Takashi Hishida ◽  
Tomoko Ohya ◽  
Yoshino Kubota ◽  
Yusuke Kamada ◽  
Hideo Shinagawa
Keyword(s):  
Dna Damage ◽  
Posttranslational Modifications ◽  
Cell Cycle Progression ◽  
Damage Tolerance ◽  
Genome Instability ◽  
Dna Helicase ◽  
Nuclear Antigen ◽  
Physical Interaction ◽  
Dna Damage Tolerance ◽  
Exogenous Dna

ABSTRACT Proliferating cell nuclear antigen (PCNA), a sliding clamp required for processive DNA synthesis, provides attachment sites for various other proteins that function in DNA replication, DNA repair, cell cycle progression and chromatin assembly. It has been shown that differential posttranslational modifications of PCNA by ubiquitin or SUMO play a pivotal role in controlling the choice of pathway for rescuing stalled replication forks. Here, we explored the roles of Mgs1 and PCNA in replication fork rescue. We provide evidence that Mgs1 physically associates with PCNA and that Mgs1 helps suppress the RAD6 DNA damage tolerance pathway in the absence of exogenous DNA damage. We also show that PCNA sumoylation inhibits the growth of mgs1 rad18 double mutants, in which PCNA sumoylation and the Srs2 DNA helicase coordinately prevent RAD52-dependent homologous recombination. The proposed roles for Mgs1, Srs2, and modified PCNA during replication arrest highlight the importance of modulating the RAD6 and RAD52 pathways to avoid genome instability.

Overexpression of the DNA mismatch repair factor, PMS2, confers hypermutability and DNA damage tolerance

2006 ◽  
Vol 244 (2) ◽  
pp. 195-202 ◽  
Author(s):  
Shannon L. Gibson ◽  
Latha Narayanan ◽  
Denise Campisi Hegan ◽  
Andrew B. Buermeyer ◽  
R. Michael Liskay ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mismatch Repair ◽  
Damage Tolerance ◽  
Dna Mismatch Repair ◽  
Dna Damage Tolerance ◽  
Dna Mismatch ◽  
Repair Factor

A Mutation in EXO1 Defines Separable Roles in DNA Mismatch Repair and a DNA Mismatch Repair-independent DNA Damage Tolerance Pathway

2005 ◽  
Vol 63 ◽  
pp. S144
Author(s):  
P.T. Tran ◽  
J. Fey ◽  
L. Gellon ◽  
S. Boiteux ◽  
Y. Chen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mismatch Repair ◽  
Damage Tolerance ◽  
Dna Mismatch Repair ◽  
Dna Damage Tolerance ◽  
Dna Mismatch

scholarly journals The Chromatin-binding Protein Spn1 contributes to Genome Instability in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Alison K. Thurston ◽  
Catherine A. Radebaugh ◽  
Adam R. Almeida ◽  
Juan Lucas Argueso ◽  
Laurie A. Stargell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Dna Damage ◽  
Genome Stability ◽  
Damage Tolerance ◽  
Genome Instability ◽  
Chromatin Binding ◽  
Dna Damage Tolerance ◽  
Template Switch

AbstractCells expend a large amount of energy to maintain their DNA sequence. DNA repair pathways, cell cycle checkpoint activation, proofreading polymerases, and chromatin structure are ways in which the cell minimizes changes to the genome. During replication, the DNA damage tolerance pathway allows the replication forks to bypass damage on the template strand. This avoids prolonged replication fork stalling, which can contribute to genome instability. The DNA damage tolerance pathway includes two sub-pathways: translesion synthesis and template switch. Post-translational modification of PCNA and the histone tails, cell cycle phase, and local DNA structure have all been shown to influence sub-pathway choice. Chromatin architecture contributes to maintaining genome stability by providing physical protection of the DNA and by regulating DNA processing pathways. As such, chromatin-binding factors have been implicated in maintaining genome stability. Using Saccharomyces cerevisiae, we examined the role of Spn1, a chromatin binding and transcription elongation factor, in DNA damage tolerance. Expression of a mutant allele of SPN1 results in increased resistance to the DNA damaging agent methyl methanesulfonate, lower spontaneous and damage-induced mutation rates, along with increased chronological lifespan. We attribute these effects to an increased usage of the template switch branch of the DNA damage tolerance pathway in the spn1 strain. This provides evidence for a role of wild type Spn1 in promoting genome instability, as well as having ties to overcoming replication stress and contributing to chronological aging.

scholarly journals Novel conserved motifs in Rev1 C-terminus are required for mutagenic DNA damage tolerance

DNA Repair ◽  
2008 ◽  
Vol 7 (9) ◽  
pp. 1455-1470 ◽  
Author(s):  
Sanjay D'Souza ◽  
Lauren S. Waters ◽  
Graham C. Walker
Keyword(s):  
Dna Damage ◽  
Damage Tolerance ◽  
Dna Damage Tolerance ◽  
Conserved Motifs ◽  
C Terminus

DNA Topoisomerases in DNA Repair and DNA Damage Tolerance

1998 ◽  
pp. 517-537 ◽  
Author(s):  
John L. Nitiss
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Damage Tolerance ◽  
Dna Damage Tolerance ◽  
Dna Topoisomerases

scholarly journals DNA-damage tolerance mediated by PCNA•Ub fusions in human cells is dependent on Rev1 but not Polη

2013 ◽  
Vol 41 (15) ◽  
pp. 7356-7369 ◽  
Author(s):  
Zhoushuai Qin ◽  
Mengxue Lu ◽  
Xin Xu ◽  
Michelle Hanna ◽  
Naoko Shiomi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Damage Tolerance ◽  
Human Cells ◽  
Dna Damage Tolerance

Deubiquitinating PCNA: a downside to DNA damage tolerance

2006 ◽  
Vol 8 (4) ◽  
pp. 303-305 ◽  
Author(s):  
Helle D. Ulrich
Keyword(s):  
Dna Damage ◽  
Damage Tolerance ◽  
Dna Damage Tolerance
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