Chromosome healing by <i>de novo</i> telomere addition in <i>Saccharomyces cerevisiae</i>

Pennaneach, Vincent; Putnam, Christopher D.; Kolodner, Richard D.

doi:10.1111/j.1365-2958.2006.05026.x

Cited by 92 publications

(92 citation statements)

References 106 publications

(185 reference statements)

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“…The two related helicases Rrm3 and Pif1 have opposing effects on rDNA breakage and recombination via their ability to regulate RFB activity (Ivessa et al 2000). Rrm3 suppresses fork stalling by driving fork progression through non-nucleosomal protein-DNA complexes (Ivessa et al 2003;Torres et al 2004a), whereas Pif1 appears to promote fork arrest, in addition to its role in suppression of de novo telomere addition (Ivessa et al 2000;Pennaneach et al 2006). The synthetic lethal interaction between dia2D and rrm3D suggests that Dia2 and Rrm3 may function redundantly to displace protein-DNA complexes, at least under some circumstances.…”

Section: Discussionmentioning

confidence: 99%

The F-Box Protein Dia2 Overcomes Replication Impedance to Promote Genome Stability in Saccharomyces cerevisiae

et al. 2006

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The maintenance of DNA replication fork stability under conditions of DNA damage and at natural replication pause sites is essential for genome stability. Here, we describe a novel role for the F-box protein Dia2 in promoting genome stability in the budding yeast Saccharomyces cerevisiae. Like most other F-box proteins, Dia2 forms a Skp1-Cdc53/Cullin-F-box (SCF) E3 ubiquitin-ligase complex. Systematic analysis of genetic interactions between dia2D and 4400 viable gene deletion mutants revealed synthetic lethal/ synthetic sick interactions with a broad spectrum of DNA replication, recombination, checkpoint, and chromatin-remodeling pathways. dia2D strains exhibit constitutive activation of the checkpoint kinase Rad53 and elevated counts of endogenous DNA repair foci and are unable to overcome MMS-induced replicative stress. Notably, dia2D strains display a high rate of gross chromosomal rearrangements (GCRs) that involve the rDNA locus and an increase in extrachromosomal rDNA circle (ERC) formation, consistent with an observed enrichment of Dia2 in the nucleolus. These results suggest that Dia2 is essential for stable passage of replication forks through regions of damaged DNA and natural fragile regions, particularly the replication fork barrier (RFB) of rDNA repeat loci. We propose that the SCF Dia2 ubiquitin ligase serves to modify or degrade protein substrates that would otherwise impede the replication fork in problematic regions of the genome. Collapse of replication forks results in the formation of DNA double-strand breaks (DSBs) that can then lead to illegitimate recombination and genome rearrangements, both of which are thought to be underlying causes of many human cancers (Lengauer et al. 1998). Physical impediments to replication fork progression include tightly bound non-nucleosomal protein-DNA complexes, DNA secondary structures, and regions of DNA damage, whereas inadequate dNTP pools cause forks to slow and eventually stall in a non-locus-specific manner (Branzei and Foiani 2005). Accumulated DNA damage or stalled replication forks elicit a checkpoint response that results in a delay of the cell cycle, induction of damage responsive genes, and the repair or bypass of the DNA lesion (Melo and Toczyski 2002;Branzei and Foiani 2005). The DNA damage checkpoint is activated upon detection of DNA lesions in G 1 and G 2 phase, and in S-phase the latter sometimes is referred to as the intra-S checkpoint. A second response in S-phase, referred to as the replication checkpoint, is the response to delayed DNA synthesis as caused by lowered dNTP pools upon inhibition of ribonucleotide reductase by hydroxyurea (HU). It is likely that the replication and intra-S checkpoint pathways are integrated such that the key signal is stalled or slowed replication forks, due to either dNTP shortage or collision with DNA damage. The only essential function of the S-phase checkpoint is to stabilize the fork when cells undergo replicative stress (Terceroet al. 2003) and thereby prevent the accumulation of recombinog...

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Section: Discussionmentioning

confidence: 99%

The F-Box Protein Dia2 Overcomes Replication Impedance to Promote Genome Stability in Saccharomyces cerevisiae

et al. 2006

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“…GCRs include non-reciprocal translocations, chromosome fusions, isoduplications and de novo addition of telomeres. 12 Translocations constitute a minor percentage of GCR events, whereas deletion and loss of genetic material distal to the DSB and subsequent de novo telomere addition is a major contributor to GCRs. In yeast, the telomerase complex consists of Est1p, Est2p (the catalytic component), Est3p, Sm proteins, and the TLC1 RNA.…”

Section: Introductionmentioning

confidence: 99%

Opening the DNA repair toolbox: Localization of DNA double strand breaks to the nuclear periphery

Oza¹,

Peterson²

2010

Cell Cycle

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E fficient repair of DNA double strand breaks is essential for cells to avoid increased mutation rates, genomic instability, and even cell death. Consequently, cells have evolved multiple mechanisms for rapidly repairing these DNA lesions, including error-free homologous recombination as well as error-prone pathways such as nonhomologous end joining. What happens to DSBs that are repaired inefficiently or not at all? Recently, several studies in budding yeast have shown that these more recalcitrant DSBs are localized to the nuclear periphery through interactions between the nuclear envelope protein, Mps3, and proteins associated with DSB chromatin. Why these DSBs are tethered to the nuclear periphery is still not clear, though the current view is that alternative repair pathways may be activated at the periphery in a final attempt to repair the lesion. In this Extra View, we discuss these recent reports, and we show that the Est1 component of the telomerase machinery plays an essential role in anchoring DSB chromatin to the nuclear envelope protein, Mps3.

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“…The PIF1 helicase subfamily appears to perform many cellular functions, ranging from nuclear DNA replication, 15 telomere length regulation, [12][13][14]26,29,30 mitochondrial genome integrity, [7][8][9][10][11]20 DNA repair, [8][9][10] Okazaki fragment processing, 16 assisting the replication fork progress through nonnucleosomal protein-DNA complexes.…”

Section: Disclosure Of Potential Conflicts Of Interestmentioning

confidence: 99%

Determination of the biochemical properties of full-length human PIF1 ATPase

Wang

et al. 2013

Prion

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Chromosome healing by de novo telomere addition in Saccharomyces cerevisiae

Cited by 92 publications

References 106 publications

The F-Box Protein Dia2 Overcomes Replication Impedance to Promote Genome Stability in Saccharomyces cerevisiae

The F-Box Protein Dia2 Overcomes Replication Impedance to Promote Genome Stability in Saccharomyces cerevisiae

Opening the DNA repair toolbox: Localization of DNA double strand breaks to the nuclear periphery

Determination of the biochemical properties of full-length human PIF1 ATPase

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