Histone H4 and the maintenance of genome integrity.

Megee, Paul C.; Morgan, Brian A.; Smith, M. Mitchell

doi:10.1101/gad.9.14.1716

Cited by 158 publications

(118 citation statements)

References 84 publications

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“…However, the K16 mutation to arginine is apparently the only single mutation that shows a clear significant increase in Sphase length (around 10 min longer) and a decrease in G 2 /M (around 7 min) (Megee et al, 1990(Megee et al, , 1995.…”

Section: Histone H4 Lysine 16 Acetylationmentioning

confidence: 97%

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

2007

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Histone deacetylases (HDACs) catalyse the removal of acetyl groups from the N-terminal tails of histones. All known HDACs can be categorized into one of four classes (I-IV). The class III HDAC or silencing information regulator 2 (Sir2) family exhibits characteristics consistent with a distinctive role in regulation of chromatin structure. Accumulating data suggest that these deacetylases acquired new roles as genomic complexity increased, including deacetylation of non-histone proteins and functional diversification in mammals. However, the intrinsic regulation of chromatin structure in species as diverse as yeast and humans, underscores the pressure to conserve core functions of class III HDACs, which are also known as Sirtuins. One of the key factors that might have contributed to this preservation is the intimate relationship between some members of this group of proteins (SirT1, SirT2 and SirT3) and deacetylation of a specific residue in histone H4, lysine 16 (H4K16). Evidence accumulated over the years has uncovered a unique role for H4K16 in chromatin structure throughout eukaryotes. Here, we review the recent findings about the functional relationship between H4K16 and the Sir2 class of deacetylases and how that relationship might impact aging and diseases including cancer and diabetes.

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Section: Histone H4 Lysine 16 Acetylationmentioning

confidence: 97%

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

2007

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“…The essential role of the acetylation of histone H4 lysines and its importance in maintaining the genome integrity came from three studies in the early 1990s. These studies showed that cells bearing several different mutations in the N termini of histone H4 exhibit cell cycle arrest at G 2 /M phase and compromised genomic stability (Megee et al, 1990(Megee et al, , 1995Durrin et al, 1991;Morgan et al, 1991). However, one of the first evidences of the involvement of histone acetylation in DNA repair was provided by Nakatani and collaborators who showed that Tip60 HAT was involved in DNA repair and that mutations in the acetylase activity of Tip60 resulted in cells with deficient DNA repair (Ikura et al, 2000).…”

Section: Dna Repairmentioning

confidence: 99%

Orchestration of chromatin-based processes: mind the TRRAP

et al. 2007

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Chromatin modifications at core histones including acetylation, methylation, phosphorylation and ubiquitination play an important role in diverse biological processes. Acetylation of specific lysine residues within the N terminus tails of core histones is arguably the most studied histone modification; however, its precise roles in different cellular processes and how it is disrupted in human diseases remain poorly understood. In the last decade, a number of histone acetyltransferases (HATs) enzymes responsible for histone acetylation, has been identified and functional studies have begun to unravel their biological functions. The activity of many HATs is dependent on HAT complexes, the multiprotein assemblies that contain one HAT catalytic subunit, adapter proteins, several other molecules of unknown function and a large protein called TRansformation/tRanscription domain-Associated Protein (TRRAP). As a common component of many HAT complexes, TRRAP appears to be responsible for the recruitment of these complexes to chromatin during transcription, replication and DNA repair. Recent studies have shed new light on the role of TRRAP in HAT complexes as well as mechanisms by which it mediates diverse cellular processes. Thus, TRRAP appears to be responsible for a concerted and context-dependent recruitment of HATs and coordination of distinct chromatin-based processes, suggesting that its deregulation may contribute to diseases. In this review, we summarize recent developments in our understanding of the function of TRRAP and TRRAP-containing HAT complexes in normal cellular processes and speculate on the mechanism underlying abnormal events that may lead to human diseases such as cancer.

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“…Isolation of RNA and Northern blot analysis were carried out as described (Megee et al 1995). PDS1 mRNA was detected using a radiolabeled DNA fragment containing the PDS1 open reading frame.…”

Section: Other Methodsmentioning

confidence: 99%

Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p.

Cohen-Fix¹,

Peters²,

Kirschner³

et al. 1996

Genes Dev.

753

645

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Anaphase initiation has been postulated to be controlled through the ubiquitin-dependent proteolysis of an unknown inhibitor. This process involves the anaphase promoting complex (APC), a specific ubiquitin ligase that has been shown to be involved in mitotic cyclin degradation. Previous studies demonstrated that in The metaphase to anaphase transition is an important step in the eukaryotic cell cycle. This process is believed to be regulated, at least in part, through sister chromatid pairing (for review, see Holm 1994; Miyazaki and OrrWeaver 1994). Sister chromatid pairing is thought to be mediated by cohesion factors that act as a "molecular glue" in associating the sister chromatids along their entire length. These cohesion factors counteract the poleward forces exerted by spindle motors, thereby preventing precocious sister chromatid separation. At metaphase, the replicated and paired sister chromatids congress to the spindle midzone through their bipolar attachments to the spindle microtubules. At anaphase, the cohesion factors are inactivated and the sister chromatids separate synchronously and move to opposite poles by means of their spindle attachment. Misregulation of the cohesion factors could lead to precocious sister chromatid separation. If this occurs prior to the formation of a stable bipolar spindle attachment, the separated chromatids would not be identified as sisters, thereby diminishing the cell's ability to segregate the two sister chromatids to opposite poles. Anaphase initiation is also controlled by checkpoints that arrest the

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Histone H4 and the maintenance of genome integrity.

Cited by 158 publications

References 84 publications

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

Orchestration of chromatin-based processes: mind the TRRAP

Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p.

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