PMID:28416769

Citation	Chitale, S and Richly, H' (2017) Nuclear organization of nucleotide excision repair is mediated by RING1B dependent H2A-ubiquitylation. Oncotarget '
Abstract	One of the major cellular DNA repair pathways is nucleotide excision repair (NER). It is the primary pathway for repair of various DNA lesions caused by exposure to ultraviolet (UV) light, such as cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts. Although lesion-containing DNA associates with the nuclear matrix after UV irradiation it is still not understood how nuclear organization affects NER. Analyzing unscheduled DNA synthesis (UDS) indicates that NER preferentially occurs in specific nuclear areas, viz the nucleolus. Upon inducing localized damage, we observe migration of damaged DNA towards the nucleolus. Employing a LacR-based tethering system we demonstrate that H2A-ubiquitylation via the UV-RING1B complex localizes chromatin close to the nucleolus. We further show that the H2A-ubiquitin binding protein ZRF1 resides in the nucleolus, and that it anchors ubiquitylated chromatin along with XPC. Our data thus provide insight into the sub-nuclear organization of NER and reveal a novel role for histone H2A-ubiquitylation.
Links	PubMed Online version:10.18632/oncotarget.16142
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:XPA	Colocalizes with	GO:0005730: nucleolus	ECO:0000314:		C		UniProt’s Protein Name: DNA repair protein complementing XP-A cells. Paper’s Protein Name: XPA. Organism: Homo sapiens. Notes: Figure 1C is used. According to the paper, the researchers “observed a distinct enrichment of XPA, a critical NER protein [1] in the nucleolus of pre-extracted U2OS and MRC5 cells, starting at 1 hour after UV irradiation.” This can indeed be seen in the cell visualization for Figure 1C. As this only occur after one hour of UV irradiation, the relationship between this protein and the nucleolus is quite clearly transient, and the Colocalizes with qualifier is necessary. U2OS and MRC5 cells are human cells, so the protein is human as well.	complete CACAO 12679
HUMAN:DNJC2		GO:0005730: nucleolus	ECO:0000314:		C		Paper’s Protein Name: H2A-ubiquitin binding protein ZRF1. UniProt’s Protein Name: DnaJ homolog subfamily C member 2 or alternatively Zuotin-related factor 1. Organism: Homo sapiens. Notes: Figure 5A is used. While “investigating the nuclear distribution of ZRF1 after pre-extraction of U2OS cells, [the researchers] detected ZRF1 in the nucleolus as seen by simultaneous Nucleophosmin (NPM) staining.” This can indeed be seen in the cell visualization for Figure 5A. This protein was present even prior to UV irradiation, so the relationship between the protein and nucleolus is not transient, and the Colocalizes With qualifier is not necessary. U2OS cells are human cells, so the protein is human as well.	complete CACAO 12680

References

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