scholarly journals Expression of a germline variant in the N-terminal domain of the human DNA glycosylase NTHL1 induces cellular transformation without impairing enzymatic function or substrate specificity

Oncotarget ◽  
2020 ◽  
Vol 11 (24) ◽  
pp. 2262-2272
Author(s):  
Carolyn G. Marsden ◽  
Pawel Jaruga ◽  
Erdem Coskun ◽  
Robyn L. Maher ◽  
David S. Pederson ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Cellular Transformation ◽  
Dna Glycosylase ◽  
Terminal Domain ◽  
Enzymatic Function ◽  
Germline Variant ◽  
Human Dna

scholarly journals The C-terminal Domain (CTD) of Human DNA Glycosylase NEIL1 Is Required for Forming BERosome Repair Complex with DNA Replication Proteins at the Replicating Genome

2015 ◽  
Vol 290 (34) ◽  
pp. 20919-20933 ◽  
Author(s):  
Pavana M. Hegde ◽  
Arijit Dutta ◽  
Shiladitya Sengupta ◽  
Joy Mitra ◽  
Sanjay Adhikari ◽  
...  
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
Dna Glycosylase ◽  
Nuclear Antigen ◽  
Replication Factor C ◽  
Replication Factor ◽  
Terminal Domain ◽  
Human Dna ◽  
Factor C

The human DNA glycosylase NEIL1 was recently demonstrated to initiate prereplicative base excision repair (BER) of oxidized bases in the replicating genome, thus preventing mutagenic replication. A significant fraction of NEIL1 in cells is present in large cellular complexes containing DNA replication and other repair proteins, as shown by gel filtration. However, how the interaction of NEIL1 affects its recruitment to the replication site for prereplicative repair was not investigated. Here, we show that NEIL1 binarily interacts with the proliferating cell nuclear antigen clamp loader replication factor C, DNA polymerase δ, and DNA ligase I in the absence of DNA via its non-conserved C-terminal domain (CTD); replication factor C interaction results in ∼8-fold stimulation of NEIL1 activity. Disruption of NEIL1 interactions within the BERosome complex, as observed for a NEIL1 deletion mutant (N311) lacking the CTD, not only inhibits complete BER in vitro but also prevents its chromatin association and reduced recruitment at replication foci in S phase cells. This suggests that the interaction of NEIL1 with replication and other BER proteins is required for efficient repair of the replicating genome. Consistently, the CTD polypeptide acts as a dominant negative inhibitor during in vitro repair, and its ectopic expression sensitizes human cells to reactive oxygen species. We conclude that multiple interactions among BER proteins lead to large complexes, which are critical for efficient BER in mammalian cells, and the CTD interaction could be targeted for enhancing drug/radiation sensitivity of tumor cells.

scholarly journals The Disordered C-Terminal Domain of Human DNA Glycosylase NEIL1 Contributes to Its Stability via Intramolecular Interactions

2013 ◽  
Vol 425 (13) ◽  
pp. 2359-2371 ◽  
Author(s):  
Muralidhar L. Hegde ◽  
Susan E. Tsutakawa ◽  
Pavana M. Hegde ◽  
Luis Marcelo F. Holthauzen ◽  
Jing Li ◽  
...  
Keyword(s):  
Intramolecular Interactions ◽  
Dna Glycosylase ◽  
Terminal Domain ◽  
Human Dna

scholarly journals Substrate Specificity of the FurE Transporter Is Determined by Cytoplasmic Terminal Domain Interactions

Genetics ◽  
2017 ◽  
pp. genetics.300327.2017 ◽  
Author(s):  
Georgia F. Papadaki ◽  
Sotiris Amillis ◽  
George Diallinas
Keyword(s):  
Substrate Specificity ◽  
Terminal Domain ◽  
Domain Interactions

scholarly journals Germ-line variant of human NTH1 DNA glycosylase induces genomic instability and cellular transformation

2013 ◽  
Vol 110 (35) ◽  
pp. 14314-14319 ◽  
Author(s):  
H. A. Galick ◽  
S. Kathe ◽  
M. Liu ◽  
S. Robey-Bond ◽  
D. Kidane ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Germ Line ◽  
Cellular Transformation ◽  
Dna Glycosylase

scholarly journals The Carboxy-Terminal Domain of ROS1 Is Essential for 5-Methylcytosine DNA Glycosylase Activity

2014 ◽  
Vol 426 (22) ◽  
pp. 3703-3712 ◽  
Author(s):  
Samuel Hong ◽  
Hideharu Hashimoto ◽  
Yoke Wah Kow ◽  
Xing Zhang ◽  
Xiaodong Cheng
Keyword(s):  
Dna Glycosylase ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Carboxy Terminal

scholarly journals Expression and purification of NEIL3, a human DNA glycosylase homolog

2009 ◽  
Vol 65 (2) ◽  
pp. 160-164 ◽  
Author(s):  
Silje Z. Krokeide ◽  
Nils Bolstad ◽  
Jon K. Laerdahl ◽  
Magnar Bjørås ◽  
Luisa Luna
Keyword(s):  
Dna Glycosylase ◽  
Expression And Purification ◽  
Human Dna
Sign in / Sign up

Export Citation Format

Share Document