TDP1 and TDP2 process unligatable DSB ends

Stable Identifier
Reaction [transition]
Homo sapiens
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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
24236237 Processing of damaged DNA ends for double-strand break repair in mammalian cells

Povirk, LF

ISRN Mol Biol 2012
25841101 TDP1 promotes assembly of non-homologous end joining protein complexes on DNA

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

DNA Repair (Amst.) 2015
19505854 Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

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

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

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

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

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

PLoS Genet. 2013
Catalyst Activity

phosphoric diester hydrolase activity of (TDP1,TDP2) [nucleoplasm]

Orthologous Events
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