Histone Acetylation Regulates the Time of Replication Origin Firing

Vogelauer, Maria; Rubbi, Liudmilla; Lucas, Isabelle; Brewer, Bonita J.; Grunstein, Michael

doi:10.1016/s1097-2765(02)00702-5

Cited by 380 publications

(391 citation statements)

References 52 publications

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“…Interestingly, HBO1 HAT, similar to TIP60, is able to acetylate all four lysines in histone H4 tail, although it localizes differently from Tip60 HAT (Doyon et al, 2006), suggesting that certain HATs may be more important in replication than in other chromatin-based processes such as transcription. In addition, a correlation between histone acetylation, transcriptional competence and DNA replication timing was also found in several studies using cells with different levels of pluripotency (Vogelauer et al, 2002;Zhang et al, 2002;Lin et al, 2003;Perry et al, 2004;Azuara et al, 2006). Different chromatin-based processes including transcription, replication and DNA repair require an open chromatin structure and are mediated by TRRAPcontaining HAT complexes, indicating that these chromatin modifiers regulate distinct and often conflicting processes.…”

Section: Replicationmentioning

confidence: 63%

“…Although the role of chromatin modifications in replication is still poorly understood, recent studies provide evidence that post-translational chromatin modifications can control the efficiency and/or timing of replication origin activity (Vogelauer et al, 2002;Zhang et al, 2002;Kurdistani and Grunstein, 2003;Lin et al, 2003;Perry et al, 2004;Azuara et al, 2006). In yeast, histone acetylation in the vicinity of replication origin is an important determinant of replication timing and it appears that higher level of histone acetylation coincides with earlier firing of an origin (Vogelauer et al, 2002).…”

Section: Replicationmentioning

confidence: 99%

“…In yeast, histone acetylation in the vicinity of replication origin is an important determinant of replication timing and it appears that higher level of histone acetylation coincides with earlier firing of an origin (Vogelauer et al, 2002). However, the role of acetylation in replication timing may not be limited to yeast.…”

Section: Replicationmentioning

confidence: 99%

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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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Section: Replicationmentioning

confidence: 63%

Section: Replicationmentioning

confidence: 99%

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Orchestration of chromatin-based processes: mind the TRRAP

et al. 2007

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“…The histone acetylation level is one of the marks that distinguish early-and late-replicating regions. For instance, in early S phase, histones H3 and H4 embedded in chromatin are generally hyperacetylated, whereas in late S phase they are hypoacetylated 14,15 , regulating the time of replication origin firing 15 . We thus examined whether the observed hypoacetylation of histones induced by the curcumin-mediated inhibition of the p300 HAT activity, might be responsible for an alteration of the replication timing.…”

Section: Resultsmentioning

confidence: 99%

“…For instance, in early S phase, histones H3 and H4 embedded in chromatin are generally hyperacetylated, whereas in late S phase they are hypoacetylated, regulating the time of replication origin firing 14,15 . Because the replication time is coordinately regulated at the level of large megabase-sized domains, a change in replication timing would rapidly transmit a change in chromatin state to entire chromosomal domains, that could be responsible for the formation of SAHF and then to the senescence-induced growth arrest.…”

Section: Resultsmentioning

confidence: 99%

p53 and p16INK4A independent induction of senescence by chromatin-dependent alteration of S-phase progression

et al. 2011

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senescence is triggered by various cellular stresses that result in genomic lesions and DnA damage response activation. However, the role of chromatin and DnA replication in senescence induction remains elusive. Here we show that downregulation of p300 histone acetyltransferase activity induces senescence by a mechanism that is independent of the activation of p53, p21 CIP1 and p16 InK4A . This inhibition leads to a global H3, H4 hypoacetylation, initiating senescence-associated heterochromatic foci formation during s phase, together with a global decrease in replication fork velocity, and alteration of DnA replication timing. This replicative stress occurs without DnA damage and checkpoint activation, but results in a robust G2/m cell cycle arrest, within only one cell cycle. These results provide new insights into the control of s-phase progression by p300, and identify an unexpected chromatindependent alternative mechanism for senescence induction, which could possibly be exploited to treat cancer by senescence induction without generating further DnA damage.

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Eukaryotic Replication Origins and Initiation of DNA Replication

DePamphilis¹,

Aladjem²

2010

Encyclopedia of Life Sciences

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Eukaryotic deoxyribonucleic acid (DNA) replication begins at specific genomic sites called replication origins that serve as assembly sites for prereplication complexes (preRCs). PreRCs include proteins that recognise origin sequences, helicases that separate the two strands of DNA and accessory proteins that facilitate helicase binding and interaction with cell cycle regulatory pathways. Assembly of preRCs is required for initiation of DNA replication which occurs after those complexes recruit additional proteins including DNA polymerases . The sequence requirements for replication origins vary but they all include several distinct DNA elements that act synergistically to facilitate preRC assembly. The number of potential replication origins is higher than the number of actual replication initiation sites. Epigenetic processes and metabolic conditions dynamically select the location of replication initiation events of each cell cycle to insure complete and accurate replication of the entire genome in coordination with gene expression and chromatin condensation. Key Concepts: Replication initiates at distinct chromosomal locations that recruit prereplication (preRC) complexes. PreRCs are recruited sequentially, each step subject to strict regulation to prevent rereplication. Cyclin‐dependent kinases (CDK) levels change during the cell cycle. Low CDK activity is required for preRC assembly as cells exit mitosis. High CDK activity is required for activation of existing preRCs and initiation of DNA synthesis, while simultaneously suppressing assembly of new preRCs. Replication origin sequences vary among metazoans, but the functions of proteins that bind replication origins are conserved. Eukaryotic origins exhibit a modular structure. Modularity is detectable in single‐cell eukaryotes such as yeast and is more pronounced in metazoans, in which replication origins often cluster. Not all potential replication origins are activated in each cell cycle. Utilisation of replication origins is regulated dynamically to facilitate coordination with other metabolic processes occurring on chromatin. Either hyperactivation or suppression of replication origins can damage DNA and cause chromosomal rearrangements, suggesting that spacing replication initiation events at defined intervals facilitates genomic stability.

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Histone Acetylation Regulates the Time of Replication Origin Firing

Cited by 380 publications

References 52 publications

Orchestration of chromatin-based processes: mind the TRRAP

Orchestration of chromatin-based processes: mind the TRRAP

p53 and p16INK4A independent induction of senescence by chromatin-dependent alteration of S-phase progression

Eukaryotic Replication Origins and Initiation of DNA Replication

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