Histone H3 lysine 56 acetylation and the response to DNA replication fork damage
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Histone H3 lysine 56 acetylation and the response to DNA replication fork damage. / Wurtele, Hugo; Kaiser, Gitte Schalck; Bacal, Julien; St-Hilaire, Edlie; Lee, Eun-Hye; Tsao, Sarah; Dorn, Jonas; Maddox, Paul; Lisby, Michael; Pasero, Philippe; Verreault, Alain.
I: Molecular and Cellular Biology, Bind 32, Nr. 1, 2012, s. 154-172.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Histone H3 lysine 56 acetylation and the response to DNA replication fork damage
AU - Wurtele, Hugo
AU - Kaiser, Gitte Schalck
AU - Bacal, Julien
AU - St-Hilaire, Edlie
AU - Lee, Eun-Hye
AU - Tsao, Sarah
AU - Dorn, Jonas
AU - Maddox, Paul
AU - Lisby, Michael
AU - Pasero, Philippe
AU - Verreault, Alain
PY - 2012
Y1 - 2012
N2 - In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) occurs in newly synthesized histones that are deposited throughout the genome during DNA replication. Defects in H3K56ac sensitize cells to genotoxic agents, suggesting that this modification plays an important role in the DNA damage response. However, the links between histone acetylation, the nascent chromatin structure, and the DNA damage response are poorly understood. Here we report that cells devoid of H3K56ac are sensitive to DNA damage sustained during transient exposure to methyl methanesulfonate (MMS) or camptothecin but are only mildly affected by hydroxyurea. We demonstrate that, after exposure to MMS, H3K56ac-deficient cells cannot complete DNA replication and eventually segregate chromosomes with intranuclear foci containing the recombination protein Rad52. In addition, we provide evidence that these phenotypes are not due to defects in base excision repair, defects in DNA damage tolerance, or a lack of Rad51 loading at sites of DNA damage. Our results argue that the acute sensitivity of H3K56ac-deficient cells to MMS and camptothecin stems from a failure to complete the repair of specific types of DNA lesions by recombination and/or from defects in the completion of DNA replication.
AB - In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) occurs in newly synthesized histones that are deposited throughout the genome during DNA replication. Defects in H3K56ac sensitize cells to genotoxic agents, suggesting that this modification plays an important role in the DNA damage response. However, the links between histone acetylation, the nascent chromatin structure, and the DNA damage response are poorly understood. Here we report that cells devoid of H3K56ac are sensitive to DNA damage sustained during transient exposure to methyl methanesulfonate (MMS) or camptothecin but are only mildly affected by hydroxyurea. We demonstrate that, after exposure to MMS, H3K56ac-deficient cells cannot complete DNA replication and eventually segregate chromosomes with intranuclear foci containing the recombination protein Rad52. In addition, we provide evidence that these phenotypes are not due to defects in base excision repair, defects in DNA damage tolerance, or a lack of Rad51 loading at sites of DNA damage. Our results argue that the acute sensitivity of H3K56ac-deficient cells to MMS and camptothecin stems from a failure to complete the repair of specific types of DNA lesions by recombination and/or from defects in the completion of DNA replication.
KW - Acetylation
KW - Antineoplastic Agents
KW - Camptothecin
KW - DNA Damage
KW - DNA Repair
KW - DNA Replication
KW - DNA, Fungal
KW - Histones
KW - Hydroxyurea
KW - Lysine
KW - Methyl Methanesulfonate
KW - Mutagens
KW - Mutation
KW - Saccharomyces cerevisiae
KW - Saccharomyces cerevisiae Proteins
U2 - 10.1128/MCB.05415-11
DO - 10.1128/MCB.05415-11
M3 - Journal article
C2 - 22025679
VL - 32
SP - 154
EP - 172
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 1
ER -
ID: 43222908