Ubiquitin and ubiquitin-like molecules in DNA double strand break repair

Yu, Jia; Qin, Bo; Lou, Zhenkun

doi:10.1186/s13578-020-0380-1

Cited by 30 publications

(21 citation statements)

References 168 publications

(186 reference statements)

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“…Ubiquitination of proteins at DSB sites has been extensively studied and shown to play important roles in DSB response. These roles include promoting the recruitment of checkpoint and repair proteins at damage sites, altering protein–protein interactions, and clearing repair signaling ( 28 , 29 ). In this study, we observed K48-linked ubiquitination of Nbs1, which appeared to be responsible for premature disassembly of the MRN complex from DSB sites in RecQL4-defective cells.…”

Section: Discussionmentioning

confidence: 99%

Stable maintenance of the Mre11-Rad50-Nbs1 complex is sufficient to restore the DNA double-strand break response in cells lacking RecQL4 helicase activity

Kim

Choi

et al. 2021

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Stable maintenance of the Mre11-Rad50-Nbs1 complex is sufficient to restore the DNA double-strand break response in cells lacking RecQL4 helicase activity

Kim

Choi

et al. 2021

Journal of Biological Chemistry

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“…The signal transduction inherent to the Early response to many DSBs is largely carried out by ataxia-telangiectasia mutated (ATM) protein kinase (see below, Figure 1C, and Savitsky et al, 1995;Ziv et al, 1997;Shiloh, 2003;Falck et al, 2005;Maréchal and Zou, 2013). At DSBs, ATM is the apical kinase, phosphorylating many substrates and triggering complex downstream post translational modifications (PTMs), including additional phosphorylation events, as well as methylation, ubiquitination (also known as ubiquitylation), neddylation, fatylation, ufmylation, and sumoylation of substrates (Matsuoka et al, 2007;Mu et al, 2007;Bensimon et al, 2010;Dou et al, 2011;Brown and Jackson, 2015;Yu et al, 2020).…”

Section: Introduction To Dna Damage Responsesmentioning

confidence: 99%

Immediate-Early, Early, and Late Responses to DNA Double Stranded Breaks

Kieffer

Lowndes

2022

Front. Genet.

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Loss or rearrangement of genetic information can result from incorrect responses to DNA double strand breaks (DSBs). The cellular responses to DSBs encompass a range of highly coordinated events designed to detect and respond appropriately to the damage, thereby preserving genomic integrity. In analogy with events occurring during viral infection, we appropriate the terms Immediate-Early, Early, and Late to describe the pre-repair responses to DSBs. A distinguishing feature of the Immediate-Early response is that the large protein condensates that form during the Early and Late response and are resolved upon repair, termed foci, are not visible. The Immediate-Early response encompasses initial lesion sensing, involving poly (ADP-ribose) polymerases (PARPs), KU70/80, and MRN, as well as rapid repair by so-called ‘fast-kinetic’ canonical non-homologous end joining (cNHEJ). Initial binding of PARPs and the KU70/80 complex to breaks appears to be mutually exclusive at easily ligatable DSBs that are repaired efficiently by fast-kinetic cNHEJ; a process that is PARP-, ATM-, 53BP1-, Artemis-, and resection-independent. However, at more complex breaks requiring processing, the Immediate-Early response involving PARPs and the ensuing highly dynamic PARylation (polyADP ribosylation) of many substrates may aid recruitment of both KU70/80 and MRN to DSBs. Complex DSBs rely upon the Early response, largely defined by ATM-dependent focal recruitment of many signalling molecules into large condensates, and regulated by complex chromatin dynamics. Finally, the Late response integrates information from cell cycle phase, chromatin context, and type of DSB to determine appropriate pathway choice. Critical to pathway choice is the recruitment of p53 binding protein 1 (53BP1) and breast cancer associated 1 (BRCA1). However, additional factors recruited throughout the DSB response also impact upon pathway choice, although these remain to be fully characterised. The Late response somehow channels DSBs into the appropriate high-fidelity repair pathway, typically either ‘slow-kinetic’ cNHEJ or homologous recombination (HR). Loss of specific components of the DSB repair machinery results in cells utilising remaining factors to effect repair, but often at the cost of increased mutagenesis. Here we discuss the complex regulation of the Immediate-Early, Early, and Late responses to DSBs proceeding repair itself.

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“…More recently, other ubiquitination-like modifications (e.g., sumoylation, acetylation, ISGylation, neddylation, palmitoylation, and UFMylation) have also been discovered. The roles of these posttranslational modifications (PTMs) in a myriad of cellular processes, such as receptor internalization (endocytosis), vesicle trafficking, immune response and inflammation, DNA damage response, autophagy, and cell death, have been greatly appreciated [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

Ning

2021

Viruses

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The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers. Given their importance in antiviral immune response, viruses have evolved sophisticated immune escape strategies to subvert TRIM-mediated mechanisms. In this review, we focus on their regulation of IFN-I-mediated innate immune response, which plays key roles in antiviral and antitumor defense.

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Ubiquitin and ubiquitin-like molecules in DNA double strand break repair

Cited by 30 publications

References 168 publications

Stable maintenance of the Mre11-Rad50-Nbs1 complex is sufficient to restore the DNA double-strand break response in cells lacking RecQL4 helicase activity

Stable maintenance of the Mre11-Rad50-Nbs1 complex is sufficient to restore the DNA double-strand break response in cells lacking RecQL4 helicase activity

Immediate-Early, Early, and Late Responses to DNA Double Stranded Breaks

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

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