Journal article
The Double-Bromodomain Proteins Bdf1 and Bdf2 Modulate Chromatin Structure to Regulate S-Phase Stress Response in Schizosaccharomyces pombe
Genetics (Austin), v 190(2), pp 487-500
Feb 2012
PMID: 22095079
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Bromodomain proteins bind acetylated histones to regulate transcription. Emerging evidence suggests that histone acetylation plays an important role in DNA replication and repair, although its precise mechanisms are not well understood. Here we report studies of two double bromodomain-containing proteins, Bdf1 and Bdf2, in fission yeast. Loss of Bdf1 or Bdf2 led to a reduction in the level of histone H4 acetylation. Both
bdf1
Δ and
bdf2
Δ cells showed sensitivity to DNA damaging agents, including camptothecin, that cause replication fork breakage. Consistently, Bdf1 and Bdf2 were important for recovery of broken replication forks and suppression of DNA damage. Surprisingly, deletion of
bdf1
or
bdf2
partially suppressed sensitivity of various checkpoint mutants including
swi1
Δ,
mrc1
Δ,
cds1
Δ,
crb2
Δ,
chk1
Δ, and
rad3
Δ, to hydroxyurea, a compound that stalls replication forks and activates the Cds1-dependent S-phase checkpoint. This suppression was not due to reactivation of Cds1. Instead, we found that
bdf2
deletion alleviates DNA damage accumulation caused by defects in the DNA replication checkpoint. We also show that hydroxyurea sensitivity of
mrc1
Δ and
swi1
Δ was suppressed by mutations in histone H4 acetyltransferase subunits or histone H4. These results suggest that the double bromodomain-containing proteins modulate chromatin structure to coordinate DNA replication and S-phase stress response.
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Details
- Title
- The Double-Bromodomain Proteins Bdf1 and Bdf2 Modulate Chromatin Structure to Regulate S-Phase Stress Response in Schizosaccharomyces pombe
- Creators
- Mikael V Garabedian - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, andChiaki Noguchi - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, andMelissa A Ziegler - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, andMukund M Das - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, andTanu Singh - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, andLogan J Harper - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, andAdam R Leman - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, andLyne Khair - Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USABettina A MoserToru M NakamuraEishi Noguchi - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, and
- Publication Details
- Genetics (Austin), v 190(2), pp 487-500
- Publisher
- Genetics Society of America
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000300621200015
- Scopus ID
- 2-s2.0-84863131927
- Other Identifier
- 991014878074104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity