Histone H3.1 and H3.3 Complexes Mediate Nucleosome Assembly Pathways Dependent or Independent of DNA Synthesis

Tagami, Hideaki; Ray-Gallet, Dominique; Almouzni, Geneviève; Nakatani, Yoshihiro

doi:10.1016/s0092-8674(03)01064-x

Cited by 1,186 publications

(1,537 citation statements)

References 46 publications

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“…The conserved diglycine motif of USP1 is required for its autocleavage To determine the cleavage site of USP1, an epitope-tagged USP1 was stably expressed in HeLa cells and the isolated full-length and USP1-Trunc forms were digested with trypsin as previously described 25 . Mass spectrometric analysis of the full-length USP1 protein revealed peptides spanning its entire length (Fig.…”

Section: Degradation Of Usp1 Requires Its Own Catalytic Activitymentioning

confidence: 99%

“…Immunoprecipitations were performed in RIPA buffer with specific antibodies and protein G beads and incubated at 4 °C overnight with gentle rotation. Flag-HA tagged USP1 was purfied from HeLa nuclear extract as previously described 25 . Western blots were performed with whole-cell extracts and separated on Nupage 3-12% Tris-Acetate or 4-12% Bis-Tris gradient gels (Invitrogen).…”

Section: Triton Extraction Crosslinking Immunoprecipitation and Immmentioning

confidence: 99%

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Regulation of monoubiquitinated PCNA by DUB autocleavage

et al. 2006

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Monoubiquitination is a reversible post-translational protein modification that has an important regulatory function in many biological processes, including DNA repair. Deubiquitinating enzymes (DUBs) are proteases that are negative regulators of monoubiquitination, but little is known about their regulation and contribution to the control of conjugated-substrate levels. Here, we show that the DUB ubiquitin specific protease 1 (USP1) deubiquitinates the DNA replication processivity factor, PCNA, as a safeguard against error-prone translesion synthesis (TLS) of DNA. Ultraviolet (UV) irradiation inactivates USP1 through an autocleavage event, thus enabling monoubiquitinated PCNA to accumulate and to activate TLS. Significantly, the site of USP1 cleavage is immediately after a conserved internal ubiquitin-like diglycine (Gly-Gly) motif. This mechanism is reminiscent of the processing of precursors of ubiquitin and ubiquitin-like modifiers by DUBs. Our results define a regulatory mechanism for protein ubiquitination that involves the signal-induced degradation of an inhibitory DUB.Monoubiquitination is a highly regulated process that is conserved in all eukaryotes 1,2 and controls a broad range of cellular functions, including DNA repair. Protein monoubiquitination is a reversible post-translational event that can be influenced by the opposing activities of a ubiquitin E3 ligase and a deubiquitinating enzyme (DUB), similar to the regulation of protein phosphorylation by kinases and phosphatases 3,4 . Protein monoubiquitination regulates the rescue of stalled DNA replication forks -an important cellular process required for cell survival 5 . The E2 ubiquitin conjugating enzyme RAD6 and the E3 ligase RAD18 are conserved in both yeast and human and they coordinate and activate the monoubiquitination of PCNA in response to UV damage or stalled replication forks [6][7][8] . Recent studies have shown that polη, a specialized TLS polymerase, is recruited to the replication fork through a specific interaction with monoubiquitinated PCNA 7 . The deployment of TLS polymerases during replication ensures timely bypass of the diverse DNA lesions encountered by the replication fork. Although many TLS polymerases are intrinsically mutagenic, polη allows replication past UV-damaged bases with high fidelity 9-11 . Thus, a model has emerged in which polη binds to monoubiquitinated PCNA and ensures accurate (error-free) replicative bypass of UV lesions. However, other (error-prone) TLS polymerases (such as polι and Rev1) have recently been shown to rely on monoubiquitinated PCNA for their function 12,13 . How cells limit PCNA monoubiquitination and the unwanted deployment of polη and/or other error-prone TLS polymerases in the absence or presence of extrinsic DNA damage during the synthesis of DNA in S phase is not known.In humans, protein deubiquitination is controlled by a family of approximately 95 distinct DUB enzymes 14,15 but the function of most of these proteins is unknown. DUBs are cysteine proteases that cleave ubiquitin fro...

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Section: Degradation Of Usp1 Requires Its Own Catalytic Activitymentioning

confidence: 99%

Section: Triton Extraction Crosslinking Immunoprecipitation and Immmentioning

confidence: 99%

Regulation of monoubiquitinated PCNA by DUB autocleavage

et al. 2006

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“…Significantly, at least one of these, the histone chaperone HIRA, has been shown to increase in expression or undergo some level of regulation in aging baboon skin [40,41]. Although the HIRA histone chaperone may have some functions linked to transcription activation [42][43][44][45][46][47][48], this chaperone is known to have an evolutionarily conserved role in heterochromatin formation [49][50][51][52][53][54][55][56].…”

Section: Aging Is Associated With Epigenetic Changes From Yeast To Hmentioning

confidence: 99%

Aging by epigenetics—A consequence of chromatin damage?

Sedivy

Gowrishankar

Adams

2008

Experimental Cell Research

140

102

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Chromatin structure is not fixed. Instead, chromatin is dynamic and is subject to extensive developmental and age-associated remodeling. In some cases, this remodeling appears to counter the aging and age-associated diseases, such as cancer, and extend organismal lifespan. However, stochastic non-deterministic changes in chromatin structure might, over time, also contribute to the break down of nuclear, cell and tissue function, and consequently aging and age-associated diseases.

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“…While H3.3 differs from canonical vertebrate H3 by only four amino acids, it binds distinct histone chaperones (Szenker et al , 2011) and nucleosomes containing H3.3 are unusually sensitive to salt‐dependent disruption (Jin & Felsenfeld, 2007). Importantly, H3.3 is expressed throughout the cell cycle and can therefore be incorporated independently of S‐phase (Tagami et al , 2004). It is thus enriched in areas of increased nucleosome turnover including transcribed genes but is also found in silent regions including pericentromeric heterochromatin and telomeres (Szenker et al , 2011).…”

Section: Introductionmentioning

confidence: 99%

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID ‐accessible single‐stranded DNA

et al. 2016

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Immunoglobulin diversification is driven by activation‐induced deaminase (AID), which converts cytidine to uracil within the Ig variable (IgV) regions. Central to the recruitment of AID to the IgV genes are factors that regulate the generation of single‐stranded DNA (ssDNA), the enzymatic substrate of AID. Here, we report that chicken DT40 cells lacking variant histone H3.3 exhibit reduced IgV sequence diversification. We show that this results from impairment of the ability of AID to access the IgV genes due to reduced formation of ssDNA during IgV transcription. Loss of H3.3 also diminishes IgV R‐loop formation. However, reducing IgV R‐loops by RNase HI overexpression in wild‐type cells does not affect IgV diversification, showing that these structures are not necessary intermediates for AID access. Importantly, the reduction in the formation of AID‐accessible ssDNA in cells lacking H3.3 is independent of any effect on the level of transcription or the kinetics of RNAPII elongation, suggesting the presence of H3.3 in the nucleosomes of the IgV genes increases the chances of the IgV DNA becoming single‐stranded, thereby creating an effective AID substrate.

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Histone H3.1 and H3.3 Complexes Mediate Nucleosome Assembly Pathways Dependent or Independent of DNA Synthesis

Cited by 1,186 publications

References 46 publications

Regulation of monoubiquitinated PCNA by DUB autocleavage

Regulation of monoubiquitinated PCNA by DUB autocleavage

Aging by epigenetics—A consequence of chromatin damage?

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID ‐accessible single‐stranded DNA

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