---
DOAJ_listed: '1'
_id: '18277'
abstract:
- lang: eng
  text: Proper DNA damage repair is one of the most vital and fundamental functions
    of every cell. Several different repair mechanisms exist to deal with various
    types of DNA damage, in various stages of the cell cycle and under different conditions.
    Homologous recombination is one of the most important repair mechanisms in all
    organisms. Srs2, a regulator of homologous recombination, is a DNA helicase involved
    in DNA repair, cell cycle progression and genome integrity. Srs2 can remove Rad51
    from ssDNA, and is thought to inhibit unscheduled recombination. However, Srs2
    has to be precisely regulated, as failure to do so is toxic and can lead to cell
    death. We noticed that a very slight elevation of the levels of Srs2 (by addition
    of a single extra copy of the SRS2 gene) leads to hyper-sensitivity of yeast cells
    to methyl methanesulfonate (MMS, a DNA damaging agent). This effect is seen in
    haploid, but not in diploid, cells. We analyzed the mechanism that controls haploid/diploid
    sensitivity and arrived to the conclusion that the sensitivity requires the activity
    of RAD59 and RDH54, whose expression in diploid cells is repressed. We carried
    out a mutational analysis of Srs2 to determine the regions of the protein required
    for the sensitization to genotoxins. Interestingly, Srs2 needs the HR machinery
    and its helicase activity for its toxicity, but does not need to dismantle Rad51.
    Our work underscores the tight regulation that is required on the levels of Srs2
    activity, and the fact that Srs2 helicase activity plays a more central role in
    DNA repair than the ability of Srs2 to dismantle Rad51 filaments.
article_processing_charge: No
author:
- first_name: Alexander
  full_name: Bronstein, Alexander
  id: 58f3726e-7cba-11ef-ad8b-e6e8cb3904e6
  last_name: Bronstein
  orcid: 0000-0001-9699-8730
- first_name: Shay
  full_name: Bramson, Shay
  last_name: Bramson
- first_name: Keren
  full_name: Shemesh, Keren
  last_name: Shemesh
- first_name: Batia
  full_name: Liefshitz, Batia
  last_name: Liefshitz
- first_name: Martin
  full_name: Kupiec, Martin
  last_name: Kupiec
citation:
  ama: 'Bronstein AM, Bramson S, Shemesh K, Liefshitz B, Kupiec M. Tight regulation
    of Srs2 helicase activity is crucial for proper functioning of DNA Repair mechanisms.
    <i>G3: Genes, Genomes, Genetics </i>. 2018;8(5):1615-1626. doi:<a href="https://doi.org/10.1534/g3.118.200181">10.1534/g3.118.200181</a>'
  apa: 'Bronstein, A. M., Bramson, S., Shemesh, K., Liefshitz, B., &#38; Kupiec, M.
    (2018). Tight regulation of Srs2 helicase activity is crucial for proper functioning
    of DNA Repair mechanisms. <i>G3: Genes, Genomes, Genetics </i>. Oxford University
    Press (OUP). <a href="https://doi.org/10.1534/g3.118.200181">https://doi.org/10.1534/g3.118.200181</a>'
  chicago: 'Bronstein, Alex M., Shay Bramson, Keren Shemesh, Batia Liefshitz, and
    Martin Kupiec. “Tight Regulation of Srs2 Helicase Activity Is Crucial for Proper
    Functioning of DNA Repair Mechanisms.” <i>G3: Genes, Genomes, Genetics </i>. Oxford
    University Press (OUP), 2018. <a href="https://doi.org/10.1534/g3.118.200181">https://doi.org/10.1534/g3.118.200181</a>.'
  ieee: 'A. M. Bronstein, S. Bramson, K. Shemesh, B. Liefshitz, and M. Kupiec, “Tight
    regulation of Srs2 helicase activity is crucial for proper functioning of DNA
    Repair mechanisms,” <i>G3: Genes, Genomes, Genetics </i>, vol. 8, no. 5. Oxford
    University Press (OUP), pp. 1615–1626, 2018.'
  ista: 'Bronstein AM, Bramson S, Shemesh K, Liefshitz B, Kupiec M. 2018. Tight regulation
    of Srs2 helicase activity is crucial for proper functioning of DNA Repair mechanisms.
    G3: Genes, Genomes, Genetics . 8(5), 1615–1626.'
  mla: 'Bronstein, Alex M., et al. “Tight Regulation of Srs2 Helicase Activity Is
    Crucial for Proper Functioning of DNA Repair Mechanisms.” <i>G3: Genes, Genomes,
    Genetics </i>, vol. 8, no. 5, Oxford University Press (OUP), 2018, pp. 1615–26,
    doi:<a href="https://doi.org/10.1534/g3.118.200181">10.1534/g3.118.200181</a>.'
  short: 'A.M. Bronstein, S. Bramson, K. Shemesh, B. Liefshitz, M. Kupiec, G3: Genes,
    Genomes, Genetics  8 (2018) 1615–1626.'
date_created: 2024-10-09T07:44:48Z
date_published: 2018-05-01T00:00:00Z
date_updated: 2024-12-19T16:00:24Z
day: '01'
doi: 10.1534/g3.118.200181
extern: '1'
intvolume: '         8'
issue: '5'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1534/g3.118.200181
month: '05'
oa: 1
oa_version: Published Version
page: 1615-1626
publication: 'G3: Genes, Genomes, Genetics '
publication_identifier:
  eissn:
  - 2160-1836
publication_status: published
publisher: Oxford University Press (OUP)
quality_controlled: '1'
scopus_import: '1'
status: public
title: Tight regulation of Srs2 helicase activity is crucial for proper functioning
  of DNA Repair mechanisms
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2018'
...
---
DOAJ_listed: '1'
_id: '18437'
abstract:
- lang: eng
  text: "\r\n\r\nElg1 and Srs2 are two proteins involved in maintaining genome stability
    in yeast. After DNA damage, the homotrimeric clamp PCNA, which provides stability
    and processivity to DNA polymerases and serves as a docking platform for DNA repair
    enzymes, undergoes modification by the ubiquitin-like molecule SUMO. PCNA SUMOylation
    helps recruit Srs2 and Elg1 to the replication fork. In the absence of Elg1, both
    SUMOylated PCNA and Srs2 accumulate at the chromatin fraction, indicating that
    Elg1 is required for removing SUMOylated PCNA and Srs2 from DNA. Despite this
    interaction, which suggests that the two proteins work together, double mutants
    elg1Δ srs2Δ have severely impaired growth as haploids and exhibit synergistic
    sensitivity to DNA damage and a synergistic increase in gene conversion. In addition,
    diploid elg1Δ srs2Δ double mutants are dead, which implies that an essential function
    in the cell requires at least one of the two gene products for survival. To gain
    information about this essential function, we have carried out a high copy number
    suppressor screen to search for genes that, when overexpressed, suppress the synthetic
    lethality between elg1Δ and srs2Δ. We report the identification of 36 such genes,
    which are enriched for functions related to DNA- and chromatin-binding, chromatin
    packaging and modification, and mRNA export from the nucleus."
article_processing_charge: No
author:
- first_name: Inbal
  full_name: Gazy, Inbal
  last_name: Gazy
- first_name: Batia
  full_name: Liefshitz, Batia
  last_name: Liefshitz
- first_name: Alexander
  full_name: Bronstein, Alexander
  id: 58f3726e-7cba-11ef-ad8b-e6e8cb3904e6
  last_name: Bronstein
  orcid: 0000-0001-9699-8730
- first_name: Oren
  full_name: Parnas, Oren
  last_name: Parnas
- first_name: Nir
  full_name: Atias, Nir
  last_name: Atias
- first_name: Roded
  full_name: Sharan, Roded
  last_name: Sharan
- first_name: Martin
  full_name: Kupiec, Martin
  last_name: Kupiec
citation:
  ama: 'Gazy I, Liefshitz B, Bronstein AM, et al. A genetic screen for high copy number
    suppressors of the synthetic lethality between elg1Δ and srs2Δ in yeast. <i> G3:
    Genes, Genomes, Genetics</i>. 2013;3(5):917-926. doi:<a href="https://doi.org/10.1534/g3.113.005561">10.1534/g3.113.005561</a>'
  apa: 'Gazy, I., Liefshitz, B., Bronstein, A. M., Parnas, O., Atias, N., Sharan,
    R., &#38; Kupiec, M. (2013). A genetic screen for high copy number suppressors
    of the synthetic lethality between elg1Δ and srs2Δ in yeast. <i> G3: Genes, Genomes,
    Genetics</i>. Oxford University Press. <a href="https://doi.org/10.1534/g3.113.005561">https://doi.org/10.1534/g3.113.005561</a>'
  chicago: 'Gazy, Inbal, Batia Liefshitz, Alex M. Bronstein, Oren Parnas, Nir Atias,
    Roded Sharan, and Martin Kupiec. “A Genetic Screen for High Copy Number Suppressors
    of the Synthetic Lethality between Elg1Δ and Srs2Δ in Yeast.” <i> G3: Genes, Genomes,
    Genetics</i>. Oxford University Press, 2013. <a href="https://doi.org/10.1534/g3.113.005561">https://doi.org/10.1534/g3.113.005561</a>.'
  ieee: 'I. Gazy <i>et al.</i>, “A genetic screen for high copy number suppressors
    of the synthetic lethality between elg1Δ and srs2Δ in yeast,” <i> G3: Genes, Genomes,
    Genetics</i>, vol. 3, no. 5. Oxford University Press, pp. 917–926, 2013.'
  ista: 'Gazy I, Liefshitz B, Bronstein AM, Parnas O, Atias N, Sharan R, Kupiec M.
    2013. A genetic screen for high copy number suppressors of the synthetic lethality
    between elg1Δ and srs2Δ in yeast.  G3: Genes, Genomes, Genetics. 3(5), 917–926.'
  mla: 'Gazy, Inbal, et al. “A Genetic Screen for High Copy Number Suppressors of
    the Synthetic Lethality between Elg1Δ and Srs2Δ in Yeast.” <i> G3: Genes, Genomes,
    Genetics</i>, vol. 3, no. 5, Oxford University Press, 2013, pp. 917–26, doi:<a
    href="https://doi.org/10.1534/g3.113.005561">10.1534/g3.113.005561</a>.'
  short: 'I. Gazy, B. Liefshitz, A.M. Bronstein, O. Parnas, N. Atias, R. Sharan, M.
    Kupiec,  G3: Genes, Genomes, Genetics 3 (2013) 917–926.'
date_created: 2024-10-15T11:20:55Z
date_published: 2013-05-01T00:00:00Z
date_updated: 2024-12-18T15:30:20Z
day: '01'
doi: 10.1534/g3.113.005561
extern: '1'
intvolume: '         3'
issue: '5'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1534/g3.113.005561
month: '05'
oa: 1
oa_version: Published Version
page: 917-926
publication: ' G3: Genes, Genomes, Genetics'
publication_identifier:
  eissn:
  - 2160-1836
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: A genetic screen for high copy number suppressors of the synthetic lethality
  between elg1Δ and srs2Δ in yeast
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 3
year: '2013'
...