INO80-C and SWR-C: Guardians of the Genome

Gerhold, Christian-Benedikt; Hauer, M.; Gasser, Susan M.

doi:10.1016/j.jmb.2014.10.015

Cited by 45 publications

(46 citation statements)

References 132 publications

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“…Given that Mec1 and INO80C not only are required for the survival of chronic exposure to HU but also contribute to replication fork progression after brief exposure to acute levels of HU (Branzei and Foiani 2010;Gerhold et al 2015), we examined whether this was also true for PAF1C. We compared the resumption of replication in paf1Δ and mec1-100 mutants by FACS following a 2-h exposure to 0.2 M HU.…”

Section: Paf1 Promotes Replication Under Hu-induced Stressmentioning

confidence: 99%

“…Among these is the INO80 complex (INO80C), a 15-subunit nucleosome remodeler conserved from yeast to humans that slides and modifies the composition of nucleosomes on a DNA template (Gerhold et al 2015). INO80C both is a target of the DRC and physically associates with the downstream effector kinase Rad53/CHK2 (Morrison et al 2007;Chen et al 2010).…”

mentioning

confidence: 99%

“…INO80C both is a target of the DRC and physically associates with the downstream effector kinase Rad53/CHK2 (Morrison et al 2007;Chen et al 2010). INO80C maps to many transcription start sites in budding yeast yet also contributes to DSB repair and replication fork restart following removal of hydroxyurea (HU) (Gerhold et al 2015). Interestingly, INO80C can down-regulate transcription by repressing short-lived noncoding RNA at intergenic sites (Alcid and Tsukiyama 2014), possibly by restricting accessibility for RNA polymerase (Xue et al 2015).…”

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confidence: 99%

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Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress

et al. 2016

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Little is known about how cells ensure DNA replication in the face of RNA polymerase II (RNAPII)-mediated transcription, especially under conditions of replicative stress. Here we present genetic and proteomic analyses from budding yeast that uncover links between the DNA replication checkpoint sensor Mec1-Ddc2 (ATR-ATRIP), the chromatin remodeling complex INO80C (INO80 complex), and the transcription complex PAF1C (PAF1 complex). We found that a subset of chromatin-bound RNAPII is degraded in a manner dependent on Mec1, INO80, and PAF1 complexes in cells exposed to hydroxyurea (HU). On HU, Mec1 triggers the efficient removal of PAF1C and RNAPII from transcribed genes near early firing origins. Failure to evict RNAPII correlates inversely with recovery from replication stress: paf1Δ cells, like ino80 and mec1 mutants, fail to restart forks efficiently after stalling. Our data reveal unexpected synergies between INO80C, Mec1, and PAF1C in the maintenance of genome integrity and suggest a mechanism of RNAPII degradation that reduces transcription-replication fork collision.

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Section: Paf1 Promotes Replication Under Hu-induced Stressmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress

et al. 2016

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“…The enzymatic activities of Trrap and p400 are required for DNA damage-induced transition of repressive chromatin structure to open chromatin structure [10,97]. Both Trrap and p400 can promote the exchange of histone H2A variant H2A.Z in nucleosomes and are required for Tip60-mediated hyperacetylation of H4, which is assisted by the removal of H2A.Z from nucleosomes [10,97,104,105]. H2A.Z has~60% homology to H2A, but contains an extended acidic domain as compared with H2A [106].…”

Section: Heterochromatic Response To Dsbsmentioning

confidence: 99%

Buried territories: heterochromatic response to DNA double-strand breaks

Feng¹,

Xiang²,

Kong³

et al. 2016

ABBS

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Cellular response to DNA double-strand breaks (DSBs), the most deleterious type of DNA damage, is highly influenced by higher-order chromatin structure in eukaryotic cells. Compared with euchromatin, the compacted structure of heterochromatin not only protects heterochromatic DNA from damage, but also adds an extra layer of control over the response to DSBs occurring in heterochromatin. One key step in this response is the decondensation of heterochromatin structure. This decondensation process facilitates the DNA damage signaling and promotes proper heterochromatic DSB repair, thus helping to prevent instability of heterochromatic regions of genomes. This review will focus on the functions of the ataxia telangiectasia mutated (ATM) signaling cascade involving ATM, heterochromatin protein 1 (HP1), Krüppel-associated box (KRAB)-associated protein-1 (KAP-1), tat-interacting protein 60 (Tip60), and many other protein factors in DSB-induced decondensation of heterochromatin and subsequent repair of heterochromatic DSBs. As some subsets of DSBs may be repaired in heterochromatin independently of the ATM signaling, a possible repair model is also proposed for ATM-independent repair of these heterochromatic DSBs.

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“…In most instances, the recruitment of chromatin remodelling factors is ATM dependent and is thus encompassed within the DDR signalling response. This subject has also been reviewed previously and will not be discussed in further detail here [74][75][76][77].…”

Section: Role Of Additional Chromatin Remodelling Factors In Dsb Repairmentioning

confidence: 99%

How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability

Jeggo

Löbrich

2015

Biochemical Journal

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DNA DSBs (double-strand breaks) are a significant threat to the viability of a normal cell, since they can result in loss of genetic material if mitosis or replication is attempted in their presence. Consequently, evolutionary pressure has resulted in multiple pathways and responses to enable DSBs to be repaired efficiently and faithfully. Cancer cells, which are under pressure to gain genomic instability, have a striking ability to avoid the elegant mechanisms by which normal cells maintain genomic stability. Current models suggest that, in normal cells, DSB repair occurs in a hierarchical manner that promotes rapid and efficient rejoining first, with the utilization of additional steps or pathways of diminished accuracy if rejoining is unsuccessful or delayed. In the present review, we evaluate the fidelity of DSB repair pathways and discuss how cancer cells promote the utilization of less accurate processes. Homologous recombination serves to promote accuracy and stability during replication, providing a battlefield for cancer to gain instability. Non-homologous end-joining, a major DSB repair pathway in mammalian cells, usually operates with high fidelity and only switches to less faithful modes if timely repair fails. The transition step is finely tuned and provides another point of attack during tumour progression. In addition to DSB repair, a DSB signalling response activates processes such as cell cycle checkpoint arrest, which enhance the possibility of accurate DSB repair. We consider the ways by which cancers modify and hijack these processes to gain genomic instability.

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INO80-C and SWR-C: Guardians of the Genome

Cited by 45 publications

References 132 publications

Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress

Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress

Buried territories: heterochromatic response to DNA double-strand breaks

How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability

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