Chromatin Assembly Factor 1 Interacts with Histone H3 Methylated at Lysine 79 in the Processes of Epigenetic Silencing and DNA Repair†

Biochemistry ◽  
2006 ◽  
Vol 45 (9) ◽  
pp. 2852-2861 ◽  
Author(s):  
Hui Zhou ◽  
Benjamin J. Madden ◽  
David C. Muddiman ◽  
Zhiguo Zhang
Keyword(s):  
Dna Repair ◽  
Histone H3 ◽  
Epigenetic Silencing ◽  
Chromatin Assembly ◽  
Chromatin Assembly Factor ◽  
Assembly Factor

scholarly journals Physical and Functional Interaction between the Bloom's Syndrome Gene Product and the Largest Subunit of Chromatin Assembly Factor 1

2004 ◽  
Vol 24 (11) ◽  
pp. 4710-4719 ◽  
Author(s):  
Renjie Jiao ◽  
Csanád Z. Bachrati ◽  
Graziella Pedrazzi ◽  
Patrick Kuster ◽  
Maja Petkovic ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cancer Susceptibility ◽  
Chromatin Assembly ◽  
Bloom's Syndrome ◽  
Functional Interaction ◽  
Chromatin Assembly Factor ◽  
Bloom’S Syndrome ◽  
Hydroxyurea Treatment ◽  
Assembly Factor

ABSTRACT Bloom's syndrome (BS) is a genomic instability disorder characterized by cancer susceptibility. The protein defective in BS, BLM, belongs to the RecQ family of DNA helicases. In this study, we found that BLM interacts with hp150, the largest subunit of chromatin assembly factor 1 (CAF-1), in vitro and in vivo. Colocalization of a proportion of the cellular complement of these two proteins is found at specific nuclear foci coinciding with sites of DNA synthesis in the S phase. This colocalization increases in the presence of agents that damage DNA or inhibit DNA replication. In support of a functional interaction between BLM and CAF-1, we show that BLM inhibits CAF-1-mediated chromatin assembly during DNA repair in vitro. Although CAF-1 activity is not altered in BLM-deficient cells, the absence of BLM does impair the ability of CAF-1 to be mobilized within the nucleus in response to hydroxyurea treatment. Our results provide the first link between BLM and chromatin assembly coupled to DNA repair and suggest that BLM and CAF-1 function in a coordinated way to promote survival in response to DNA damage and/or replication blockade.

scholarly journals Role of Saccharomyces cerevisiae Chromatin Assembly Factor-I in Repair of Ultraviolet Radiation Damage in Vivo

Genetics ◽  
1999 ◽  
Vol 151 (2) ◽  
pp. 485-497 ◽  
Author(s):  
John C Game ◽  
Paul D Kaufman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Gene Silencing ◽  
Chromatin Assembly ◽  
Yeast Cells ◽  
Repair Gene ◽  
Uv Sensitivity ◽  
Factor I ◽  
Chromatin Assembly Factor ◽  
Assembly Factor

Abstract In vitro, the protein complex Chromatin Assembly Factor-I (CAF-I) from human or yeast cells deposits histones onto DNA templates after replication. In Saccharomyces cerevisiae, the CAC1, CAC2, and CAC3 genes encode the three CAF-I subunits. Deletion of any of the three CAC genes reduces telomeric gene silencing and confers an increase in sensitivity to killing by ultraviolet (UV) radiation. We used double and triple mutants involving cac1Δ and yeast repair gene mutations to show that deletion of the CAC1 gene increases the UV sensitivity of cells mutant in genes from each of the known DNA repair epistasis groups. For example, double mutants involving cac1Δ and excision repair gene deletions rad1Δ or rad14Δ showed increased UV sensitivity, as did double mutants involving cac1Δ and deletions of members of the RAD51 recombinational repair group. cac1Δ also increased the UV sensitivity of strains with defects in either the error-prone (rev3Δ) or error-free (pol30-46) branches of RAD6-mediated postreplicative DNA repair but did not substantially increase the sensitivity of strains carrying null mutations in the RAD6 or RAD18 genes. Deletion of CAC1 also increased the UV sensitivity and rate of UV-induced mutagenesis in rad5Δ mutants, as has been observed for mutants defective in error-free postreplicative repair. Together, these data suggest that CAF-I has a role in error-free postreplicative damage repair and may also have an auxiliary role in other repair mechanisms. Like the CAC genes, RAD6 is also required for gene silencing at telomeres. We find an increased loss of telomeric gene silencing in rad6Δ cac1Δ and rad18Δ cac1Δ double mutants, suggesting that CAF-I and multiple factors in the postreplicative repair pathway influence chromosome structure.

scholarly journals Insights into the molecular architecture and histone H3-H4 deposition mechanism of yeast Chromatin assembly factor 1

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Paul Victor Sauer ◽  
Jennifer Timm ◽  
Danni Liu ◽  
David Sitbon ◽  
Elisabetta Boeri-Erba ◽  
...  
Keyword(s):  
Dna Binding ◽  
Histone H3 ◽  
Chromatin Assembly ◽  
Molecular Architecture ◽  
Dna Molecules ◽  
Nucleosome Assembly ◽  
Chromatin Assembly Factor ◽  
Assembly Factor ◽  
Chaperone Complex

How the very first step in nucleosome assembly, deposition of histone H3-H4 as tetramers or dimers on DNA, is accomplished remains largely unclear. Here, we report that yeast chromatin assembly factor 1 (CAF1), a conserved histone chaperone complex that deposits H3-H4 during DNA replication, binds a single H3-H4 heterodimer in solution. We identify a new DNA-binding domain in the large Cac1 subunit of CAF1, which is required for high-affinity DNA binding by the CAF1 three-subunit complex, and which is distinct from the previously described C-terminal winged-helix domain. CAF1 binds preferentially to DNA molecules longer than 40 bp, and two CAF1-H3-H4 complexes concertedly associate with DNA molecules of this size, resulting in deposition of H3-H4 tetramers. While DNA binding is not essential for H3–H4 tetrasome deposition in vitro, it is required for efficient DNA synthesis-coupled nucleosome assembly. Mutant histones with impaired H3-H4 tetramerization interactions fail to release from CAF1, indicating that DNA deposition of H3-H4 tetramers by CAF1 requires a hierarchical cooperation between DNA binding, H3-H4 deposition and histone tetramerization.

scholarly journals Chromatin Assembly Coupled to DNA Repair: A New Role for Chromatin Assembly Factor I

Cell ◽  
1996 ◽  
Vol 86 (6) ◽  
pp. 887-896 ◽  
Author(s):  
Pierre-Henri L Gaillard ◽  
Emmanuelle M.-D Martini ◽  
Paul D Kaufman ◽  
Bruce Stillman ◽  
Ethel Moustacchi ◽  
...  
Keyword(s):  
Dna Repair ◽  
Chromatin Assembly ◽  
Factor I ◽  
Chromatin Assembly Factor ◽  
Assembly Factor

scholarly journals The Tousled-Like Kinases as Guardians of Genome Integrity

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Arrigo De Benedetti
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Histone H3 ◽  
Chromatin Assembly ◽  
Genome Integrity ◽  
Cancer Management ◽  
Damage Response ◽  
Assembly Factor ◽  
Key Issues ◽  
Cell Cycle Signaling

The Tousled-like kinases (TLKs) function in processes of chromatin assembly, including replication, transcription, repair, and chromosome segregation. TLKs interact specifically (and phosphorylate) with the chromatin assembly factor Asf1, a histone H3-H4 chaperone, histone H3 itself at Ser10, and also Rad9, a key protein involved in DNA repair and cell cycle signaling following DNA damage. These interactions are believed to be responsible for the action of TLKs in double-stranded break repair and radioprotection and also in the propagation of the DNA damage response. Hence, I propose that TLKs play key roles in maintenance of genome integrity in many organisms of both kingdoms. In this paper, I highlight key issues of the known roles of these proteins, particularly in the context of DNA repair (IR and UV), their possible relevance to genome integrity and cancer development, and as possible targets for intervention in cancer management.

scholarly journals Chromatin Assembly Factor I Mutants Defective for PCNA Binding Require Asf1/Hir Proteins for Silencing

2002 ◽  
Vol 22 (2) ◽  
pp. 614-625 ◽  
Author(s):  
Denise C. Krawitz ◽  
Tamar Kama ◽  
Paul D. Kaufman
Keyword(s):  
Histone H3 ◽  
Chromatin Assembly ◽  
Nucleosome Assembly ◽  
Factor I ◽  
Chromatin Assembly Factor ◽  
Assembly Factor ◽  
Histone Deposition ◽  
Assembly Activity ◽  
Impaired Binding

ABSTRACT Chromatin assembly factor I (CAF-I) is a conserved histone H3/H4 deposition complex. Saccharomyces cerevisiae mutants lacking CAF-I subunit genes (CAC1 to CAC3) display reduced heterochromatic gene silencing. In a screen for silencing-impaired cac1 alleles, we isolated a mutation that reduced binding to the Cac3p subunit and another that impaired binding to the DNA replication protein PCNA. Surprisingly, mutations in Cac1p that abolished PCNA binding resulted in very minor telomeric silencing defects but caused silencing to be largely dependent on Hir proteins and Asf1p, which together comprise an alternative silencing pathway. Consistent with these phenotypes, mutant CAF-I complexes defective for PCNA binding displayed reduced nucleosome assembly activity in vitro but were stimulated by Asf1p-histone complexes. Furthermore, these mutant CAF-I complexes displayed a reduced preference for depositing histones onto newly replicated DNA. We also observed a weak interaction between Asf1p and Cac2p in vitro, and we hypothesize that this interaction underlies the functional synergy between these histone deposition proteins.

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