Chromatin modifiers and remodellers in DNA repair and signalling

Jeggo, Penny A.; Downs, Jessica A.; Gasser, Susan M.

doi:10.1098/rstb.2016.0279

Cited by 19 publications

(19 citation statements)

References 45 publications

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“…The discovery of the initial recruitment of a chromatin modifier complex by MRX to a DNA break is an important mechanistic insight. In gene regulation, NuA4-dependent acetylation is known to promote the association and action of ATPdependent remodelers SWI/SNF, RSC, and SWR1 (1), and they are also implicated in DSB repair throughout eukaryotes (9,44). Resection-dependent recruitment of NuA4 seems similar to what has been reported for a host of chromatin remodeling enzymes (15), while NuA4 activity has also been shown to regulate their recruitment (7,13).…”

Section: Discussionmentioning

confidence: 81%

Phospho-dependent recruitment of the yeast NuA4 acetyltransferase complex by MRX at DNA breaks regulates RPA dynamics during resection

Cheng

Jobin-Robitaille

Billon

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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The KAT5 (Tip60/Esa1) histone acetyltransferase is part of NuA4, a large multifunctional complex highly conserved from yeast to mammals that targets lysines on H4 and H2A (X/Z) tails for acetylation. It is essential for cell viability, being a key regulator of gene expression, cell proliferation, and stem cell renewal and an important factor for genome stability. The NuA4 complex is directly recruited near DNA double-strand breaks (DSBs) to facilitate repair, in part through local chromatin modification and interplay with 53BP1 during the DNA damage response. While NuA4 is detected early after appearance of the lesion, its precise mechanism of recruitment remains to be defined. Here, we report a stepwise recruitment of yeast NuA4 to DSBs first by a DNA damage-induced phosphorylation-dependent interaction with the Xrs2 subunit of the Mre11-Rad50-Xrs2 (MRX) complex bound to DNA ends. This is followed by a DNA resection-dependent spreading of NuA4 on each side of the break along with the ssDNA-binding replication protein A (RPA). Finally, we show that NuA4 can acetylate RPA and regulate the dynamics of its binding to DNA, hence targeting locally both histone and nonhistone proteins for lysine acetylation to coordinate repair.

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Section: Discussionmentioning

confidence: 81%

Phospho-dependent recruitment of the yeast NuA4 acetyltransferase complex by MRX at DNA breaks regulates RPA dynamics during resection

Cheng

Jobin-Robitaille

Billon

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…However, the issue of repair process in the context of chromatin is not the main objective of the article. Thus, we encourage further reading on this topic [ 42 , 43 , 44 , 45 ].…”

Section: Factors That Affect Formation Of Uv Damagementioning

confidence: 99%

Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies

Kciuk

Marciniak

Kontek

2020

IJMS

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The protective ozone layer is continually depleting due to the release of deteriorating environmental pollutants. The diminished ozone layer contributes to excessive exposure of cells to ultraviolet (UV) radiation. This leads to various cellular responses utilized to restore the homeostasis of exposed cells. DNA is the primary chromophore of the cells that absorbs sunlight energy. Exposure of genomic DNA to UV light leads to the formation of multitude of types of damage (depending on wavelength and exposure time) that are removed by effectively working repair pathways. The aim of this review is to summarize current knowledge considering cellular response to UV radiation with special focus on DNA damage and repair and to give a comprehensive insight for new researchers in this field. We also highlight most important future prospects considering application of the progressing knowledge of UV response for the clinical control of diverse pathologies.

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“…The DDR process regulated by ATM and ATR is tightly coordinated also with DNA methylation, histone modifications (i.e., histone acetylation, methylation, phosphorylation, sumoylation, ubiquitination, and ADP ribosylation) and nucleosome positioning . Changes in nucleosomes composition and position are regulated by specialized ATP‐dependent chromatin remodelers ensuring the proper density and spacing of nucleosomes .…”

Section: Inhibitors Of Dna Damage Repair Kinases In Clinical Trials (mentioning

confidence: 99%

“…Changes in nucleosomes composition and position are regulated by specialized ATP‐dependent chromatin remodelers ensuring the proper density and spacing of nucleosomes . Chromatin manipulation thereby regulates gene expression, DNA repair, and genome stability . Generally, these chromatin remodelers can be grouped into four families: (i) chromodomain helicase DNA‐binding (CHD), (ii) inositol requiring 80 (INO80), (iii) switch/sucrose non‐fermentable (SWI/SNF), and (iv) imitation SWI (ISWI) class .…”

Section: Inhibitors Of Dna Damage Repair Kinases In Clinical Trials (mentioning

confidence: 99%

“…Generally, these chromatin remodelers can be grouped into four families: (i) chromodomain helicase DNA‐binding (CHD), (ii) inositol requiring 80 (INO80), (iii) switch/sucrose non‐fermentable (SWI/SNF), and (iv) imitation SWI (ISWI) class . The ATM and ATR kinases phosphorylate the INO80 complex, thus enhancing H2AX phosphorylation and DNA damage signaling . Besides, the solely ATM regulates the Brahma‐related gene 1 (BRG1), the ATPase subunit of SWI/SNF .…”

Section: Inhibitors Of Dna Damage Repair Kinases In Clinical Trials (mentioning

confidence: 99%

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Are DNA damage response kinases a target for the differentiation treatment of acute myeloid leukemia?

et al. 2018

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Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy characterized by the expansion of hematopoietic stem/progenitor cells (HPCs) blocked at different stages of maturation/differentiation.The poor outcome of AMLs necessitates therapeutic improvement. In AML, genes encoding for myeloid transcription factors, signaling receptors regulating cell proliferation, and epigenetic modifiers can be mutated by somatically acquired genetic mutations or altered by chromosomal translocations. These mutations modify chromatin organization at genes sites regulating HPCs proliferation, terminal differentiation, and DNA repair, contributing to the development and progression of the disease. The reversibility of the epigenetic modifications by drug treatment makes epigenetic changes attractive targets for AML therapeutic intervention. Recent findings underline increased DNA damage and abnormalities in the DNA damage response (DDR) as a critical feature of AML blasts. The DDR preserves cell integrity and must be tightly coordinated with DNA methylation and chromatin remodeling to ensure the accessibility to the DNA of transcription factors and repair enzymes. A crucial role in these events is played by the ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related protein (ATR) kinases, which are hyperactive in AML. Based on these findings, we hypothesize the inhibition of DNA damage kinases as an alternative or complementary strategy for the differentiation treatment of AML as it leads to a reduced ability to repair the DNA damage, and to the inhibition of specific epigenetic modifiers whose function is altered in leukemic cells. © 2018 IUBMB Life, 70(11):-specific demethylase 1; MDC1, mediator of DNA damage checkpoint protein 1; MRN, MRE11/RAD50/NBN complex; PIKK, phosphatidylinositol 3-kinase-related kinase; PML, promyelocytic leukemia; PML-NB, PML-nuclear bodies; PML-RARα, promyelocytic leukemia-retinoic acid receptor α; RPA, replication protein A, SWI/SNF, switch/sucrose non-fermentable.

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Chromatin modifiers and remodellers in DNA repair and signalling

Abstract: One contribution of 14 to a theme issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.

Cited by 19 publications

References 45 publications

Phospho-dependent recruitment of the yeast NuA4 acetyltransferase complex by MRX at DNA breaks regulates RPA dynamics during resection

Phospho-dependent recruitment of the yeast NuA4 acetyltransferase complex by MRX at DNA breaks regulates RPA dynamics during resection

Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies

Are DNA damage response kinases a target for the differentiation treatment of acute myeloid leukemia?

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