RNF168 Promotes Noncanonical K27 Ubiquitination to Signal DNA Damage

Gatti, Marco; Pinato, Sabrina; Maiolica, Alessio; Rocchio, Francesca; Prato, Maria Giulia; Aebersold, Ruedi; Penengo, Lorenza

doi:10.1016/j.celrep.2014.12.021

Cited by 164 publications

(140 citation statements)

References 34 publications

Supporting

Mentioning

138

Contrasting

Order By: Relevance

“…RNF8 or RNF168 deficient cells display impaired cellular responses to DNA damage, a defective G2/M checkpoint and increased radiosensitivity (Doil et al, 2009;Huen et al, 2007). In addition to K63 linked ubiquitination, RNF168 promotes noncanonical K27 linked ubiquitination in vivo and in vitro, and this specific ubiquitination is also required for the proper activation of the DNA damage response (Gatti et al, 2015). Additionally, the polycomb repressive complex 1, which contains Bmi1, Ring1, and Ring2, is required for H2A/H2AX ubiquitination (Bergink et al, 2006;Cao et al, 2005).…”

Section: Ubiquitinationmentioning

confidence: 99%

Histone modifications in DNA damage response

Cao

Shen

Zhu

2016

Sci. China Life Sci.

View full text Add to dashboard Cite

DNA damage is a relatively common event in eukaryotic cell and may lead to genetic mutation and even cancer. DNA damage induces cellular responses that enable the cell either to repair the damaged DNA or cope with the damage in an appropriate way. Histone proteins are also the fundamental building blocks of eukaryotic chromatin besides DNA, and many types of post-translational modifications often occur on tails of histones. Although the function of these modifications has remained elusive, there is ever-growing studies suggest that histone modifications play vital roles in several chromatin-based processes, such as DNA damage response. In this review, we will discuss the main histone modifications, and their functions in DNA damage response.DNA damage response, histone modifications, chromatin, DNA repair Citation:

show abstract

Section: Ubiquitinationmentioning

confidence: 99%

Histone modifications in DNA damage response

Cao

Shen

Zhu

2016

Sci. China Life Sci.

View full text Add to dashboard Cite

show abstract

“…Recently, Penengo and colleagues have investigated the functional relevance of different types of ubiquitylation in the DDR (Gatti et al, 2015) and observed that RNF168 promotes K27-linked polyubiquitylation of histone 2A (H2A) proteins and that this linkage represents the major ubiquitin chain type on chromatin upon DNA damage, as shown by using selected reaction-monitoring mass spectrometry. Crucial DDR mediators such as 53BP1, Rap80, RNF168 and RNF169 recognize these K27-linked ubiquitin chains on histones H2A and H2A.X, and the inability of a cell to form K27 linkages prevents activation of the DDR because mediators can no longer be recruited (Gatti et al, 2015).…”

Section: K11 Linkages In Heterotypic Ubiquitin Conjugates -A Powerfulmentioning

confidence: 99%

Ubiquitin chain diversity at a glance

Akutsu

Đikić

Bremm

2016

Journal of Cell Science

463

367

View full text Add to dashboard Cite

Ubiquitin plays an essential role in modulating protein functions, and deregulation of the ubiquitin system leads to the development of multiple human diseases. Owing to its molecular features, ubiquitin can form various homo-and heterotypic polymers on substrate proteins, thereby provoking distinct cellular responses. The concept of multifaceted ubiquitin chains encoding different functions has been substantiated in recent years. It has been established that all possible ubiquitin linkage types are utilized for chain assembly and propagation of specific signals in vivo. In addition, branched ubiquitin chains and phosphorylated ubiquitin molecules have been put under the spotlight recently. The development of novel technologies has provided detailed insights into the structure and function of previously poorly understood ubiquitin signals. In this Cell Science at a Glance article and accompanying poster, we provide an update on the complexity of ubiquitin chains and their physiological relevance.

show abstract

“…The RAP80 complex specifically deubiquitinates the Lys 63 -ubiquitin chains through the actions of its associated Zn 2ϩ -dependent deubiquitinating enzyme, BRCC36. Unresolved questions remain as to whether deubiquitinating enzyme activity serves to terminate DNA damage association by removing the Lys 63 -ubiquitin recognition signal for RAP80 or, alternatively, in a ubiquitin-editing capacity, whereby it removes Lys 63 -ubiquitin, thus allowing accumulation of either monoubiquitin or other ubiquitin topologies that have been reported at DSBs (23). That loss of any member of the RAP80 complex eliminates observable BRCA1 focus formation at DSBs raises the question of whether the RAP80 complex accounts for BRCA1 function in HR.…”

Section: Connecting Brca Network Biochemistry To the Ddrmentioning

confidence: 99%

Deciphering the BRCA1 Tumor Suppressor Network

Jiang

Greenberg

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

The BRCA1 tumor suppressor protein is a central constituent of several distinct macromolecular protein complexes that execute homology-directed DNA damage repair and cell cycle checkpoints. Recent years have borne witness to an exciting phase of discovery at the basic molecular level for how this network of DNA repair proteins acts to maintain genome stability and suppress cancer. The clinical dividends of this investment are now being realized with the approval of first-in-class BRCAtargeted therapies for ovarian cancer and identification of molecular events that determine responsiveness to these agents. Further delineation of the basic science underlying BRCA network function holds promise to maximally exploit genome instability for hereditary and sporadic cancer therapy.The breast cancer early-onset genes BRCA1 and BRCA2 were discovered by positional cloning approaches in kindreds with a high prevalence of breast and ovarian cancer. The initial lack of clarity presented by the domain structure of the proteins was remedied by a series of discoveries that revealed the proteins biochemically interact in large nuclear foci in response to DNA damage and are required to execute homology-directed DNA repair and cell cycle checkpoints (1). These observations strongly suggested that a common function in genome integrity maintenance is necessary to suppress cancer. Subsequent advances in protein purification and mass spectrometry methodologies have led to the expansion of this concept with the discovery that at least 13 different tumor suppressor proteins interact with BRCA1 and BRCA2. Despite these striking similarities, a linear model of BRCA-dependent DNA repair and tumor suppression is challenged by multiple other observations, namely, only ϳ5% of each protein exists in association with the BRCA1-BRCA2 complex, and breast cancers occurring in individuals with germ-line BRCA1 or BRCA2 mutations typically display different histopathologies and gene expression profiles. Coupled with the realization that chemoresistance mechanisms in BRCA1 and BRCA2 mutant cancers also differ, these features have inspired a network model relating BRCA molecular function in DNA repair to tumor suppression. We highlight recent insights into the BRCA tumor suppressor network and stress the connections between basic molecular knowledge of these proteins and their roles in genome integrity, tumor suppression, and response to therapy.

show abstract

RNF168 Promotes Noncanonical K27 Ubiquitination to Signal DNA Damage

Cited by 164 publications

References 34 publications

Histone modifications in DNA damage response

Histone modifications in DNA damage response

Ubiquitin chain diversity at a glance

Deciphering the BRCA1 Tumor Suppressor Network

Contact Info

Product

Resources

About