PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair

Zhao, Meimei; Geng, Rui; Guo, Xiang; Yuan, Ruoshi; Zhou, Xiao Albert; Zhong, Yanyan; Huo, Yanfei; Zhou, Mei; Shen, Qinjian; Li, Yinglu; Zhu, Wei‐Guo; Wang, Jiadong

doi:10.1016/j.celrep.2017.08.015

Cited by 65 publications

(58 citation statements)

References 48 publications

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“…We also showed that GCN5, a family member of PCAF, could not acetylate H1K85ac, which may be due to their diverse complex formation with different subunits (58,59). Interestingly, we found that PCAF is gradually recruited to chromatin during DNA damage repair, which is supported by a recent report that PCAF is recruited to UV-induced DNA damage sites (60). These data suggest that HDAC1 and PCAF are responsible for DNA damage-induced H1K85ac dynamics.…”

Section: Discussionsupporting

confidence: 87%

Histone H1 acetylation at lysine 85 regulates chromatin condensation and genome stability upon DNA damage

Dong

et al. 2018

Nucleic Acids Research

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Linker histone H1 has a key role in maintaining higher order chromatin structure and genome stability, but how H1 functions in these processes is elusive. Here, we report that acetylation of lysine 85 (K85) within the H1 globular domain is a critical post-translational modification that regulates chromatin organization. H1K85 is dynamically acetylated by the acetyltransferase PCAF in response to DNA damage, and this effect is counterbalanced by the histone deacetylase HDAC1. Notably, an acetylation-mimic mutation of H1K85 (H1K85Q) alters H1 binding to the nucleosome and leads to condensed chromatin as a result of increased H1 binding to core histones. In addition, H1K85 acetylation promotes heterochromatin protein 1 (HP1) recruitment to facilitate chromatin compaction. Consequently, H1K85 mutation leads to genomic instability and decreased cell survival upon DNA damage. Together, our data suggest a novel model whereby H1K85 acetylation regulates chromatin structure and preserves chromosome integrity upon DNA damage.

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Section: Discussionsupporting

confidence: 87%

Histone H1 acetylation at lysine 85 regulates chromatin condensation and genome stability upon DNA damage

Dong

et al. 2018

Nucleic Acids Research

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“…Thus, human premature aging disorders are strongly associated with defects in DSBR, BER, and NER . Furthermore, repair of DNA damage is an energy demanding process and it is becoming increasingly evident that DNA damage and persistent DDR‐linked cellular stress leads to mitochondrial dysfunction and metabolic defects . The following paragraphs discuss the molecular mechanisms underlying this signaling and how it relates to cellular bioenergetics/energy homeostasis and the cellular abundance of ATP and NAD + .…”

Section: Dna Damage Response Pathwaysmentioning

confidence: 99%

Toward understanding genomic instability, mitochondrial dysfunction and aging

Fakouri

Demarest

et al. 2018

The FEBS Journal

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The biology of aging is an area of intense research, and many questions remain about how and why cell and organismal functions decline over time. In mammalian cells, genomic instability and mitochondrial dysfunction are thought to be among the primary drivers of cellular aging. This review focuses on the interrelationship between genomic instability and mitochondrial dysfunction in mammalian cells and its relevance to age‐related functional decline at the molecular and cellular level. The importance of oxidative stress and key DNA damage response pathways in cellular aging is discussed, with a special focus on poly (ADP‐ribose) polymerase 1, whose persistent activation depletes cellular energy reserves, leading to mitochondrial dysfunction, loss of energy homeostasis, and altered cellular metabolism. Elucidation of the relationship between genomic instability, mitochondrial dysfunction, and the signaling pathways that connect these pathways/processes are keys to the future of research on human aging. An important component of mitochondrial health preservation is mitophagy, and this and other areas that are particularly ripe for future investigation will be discussed.

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“…Moreover, RPA1 interacts with both WRN and DNA2L, thereby stimulating WRN-mediated double-stranded DNA end unwinding and DNA2L-mediated ssDNA degradation (20). Corresponding to its multifaceted engagement in various aspects of DNA metabolism, RPA1 has been shown to be regulated by various PTMs such as acetylation, phosphorylation, ubiquitination, and SUMOylation (21)(22)(23)(24). However, whether and how Kcr regulates the function of RPA1 are unclear.…”

Section: Introductionmentioning

confidence: 99%

Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination–mediated DNA repair

Liu

et al. 2020

Sci. Adv.

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Previously, we reported that chromodomain Y-like (CDYL) acts as a crotonyl-coenzyme A hydratase and negatively regulates histone crotonylation (Kcr). However, the global CDYL-regulated crotonylome remains unclear. Here, we report a large-scale proteomics analysis for protein Kcr. We identify 14,311 Kcr sites across 3734 proteins in HeLa cells, providing by far the largest crotonylome dataset. We show that depletion of CDYL alters crotonylome landscape affecting diverse cellular pathways. Specifically, CDYL negatively regulated Kcr of RPA1, and mutation of the Kcr sites of RPA1 impaired its interaction with single-stranded DNA and/or with components of resection machinery, supporting a key role of RPA1 Kcr in homologous recombination DNA repair. Together, our study indicates that protein crotonylation has important implication in various pathophysiological processes. reveals CDYL-regulated RPA1 crotonylation in homologous recombination-mediated DNA repair.

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PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair

Cited by 65 publications

References 48 publications

Histone H1 acetylation at lysine 85 regulates chromatin condensation and genome stability upon DNA damage

Histone H1 acetylation at lysine 85 regulates chromatin condensation and genome stability upon DNA damage

Toward understanding genomic instability, mitochondrial dysfunction and aging

Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination–mediated DNA repair

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