TDP1 and TDP2 process unligatable DSB ends

Stable Identifier
R-HSA-5693578
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Free radical-induced DNA double strand breaks (DSBs) frequently have unligatable 3'-phosphoglycolate termini, while topoisomerase II (TOP2) inhibition produces unligatable 5'-ends, with a 5'-phosphotyrosil bond between the DNA DSB 5'-end and TOP2 (reviewed by Povirk 2012). Tyrosyl-DNA phosphodiesterase TDP1 is able to remove 3'-phosphoglycolate and plays an important role in non-homologous end joining (NHEJ) (Inamdar et al. 2002, Zhou et al. 2005, Zhou et al. 2009, Heo et al. 2015). Tyrosil-DNA phosphodiesterase TDP2 removes 5'-phosphotyrosine and is also involved in NHEJ (Gomez-Herreros et al. 2013).

Literature References
PubMed ID Title Journal Year
25841101 TDP1 promotes assembly of non-homologous end joining protein complexes on DNA

Heo, J, Li, J, Summerlin, M, Hays, A, Katyal, S, McKinnon, PJ, Nitiss, KC, Nitiss, JL, Hanakahi, LA

DNA Repair (Amst.) 2015
24236237 Processing of damaged DNA ends for double-strand break repair in mammalian cells

Povirk, LF

ISRN Mol Biol 2012
19505854 Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

Zhou, T, Akopiants, K, Mohapatra, S, Lin, PS, Valerie, K, Ramsden, DA, Lees-Miller, SP, Povirk, LF

DNA Repair (Amst.) 2009
12023295 Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1

Inamdar, KV, Pouliot, JJ, Zhou, T, Lees-Miller, SP, Rasouli-Nia, A, Povirk, LF

J Biol Chem 2002
23505375 TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo

Gómez-Herreros, F, Romero-Granados, R, Zeng, Z, Alvarez-Quilón, A, Quintero, C, Ju, L, Umans, L, Vermeire, L, Huylebroeck, D, Caldecott, KW, Cortés-Ledesma, F

PLoS Genet. 2013
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
phosphoric diester hydrolase activity of (TDP1,TDP2) [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created