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PARP1–TDP1 coupling for the repair of topoisomerase I–induced DNA damage

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Title PARP1–TDP1 coupling for the repair of topoisomerase I–induced DNA damage
 
Creator Das, Benu Brata
Huang, Shar-yin N
Murai, Junko
Christophe , Ishita Rehman
Ame, Jean-
Sengupta, Souvik
Das, Subhendu K
Majumdar, Papiya
Zhang, Hongliang
Biard, Denis
Majumder, Hemanta K
Schreiber, Vale´ rie
Pommier, Yves
 
Subject Infectious Diseases and Immunology
 
Description Poly(ADP-ribose) polymerases (PARP) attach poly(ADP-ribose) (PAR) chains to various proteins including themselves and chromatin. Topoisomerase I(Top1) regulates DNA supercoiling and is the targetof camptothecin and indenoisoquinoline anticancer drugs, as it forms Top1 cleavage complexes
(Top1cc) that are trapped by the drugs. Endogenous
and carcinogenic DNA lesions can also trap Top1cc.
Tyrosyl-DNA phosphodiesterase 1 (TDP1), a key
repair enzyme for trapped Top1cc, hydrolyzes the
phosphodiester bond between the DNA 30-end and
the Top1 tyrosyl moiety. Alternative repair pathways
for Top1cc involve endonuclease cleavage. However,
it is unknown what determines the choice between
TDP1 and the endonuclease repair pathways. Here
we show that PARP1 plays a critical role in this
process. By generating TDP1 and PARP1 doubleknockout
lymphoma chicken DT40 cells, we demonstrate
that TDP1 and PARP1 are epistatic for the
repair of Top1cc. The N-terminal domain of TDP1
directly binds the C-terminal domain of PARP1, and
TDP1 is PARylated by PARP1. PARylation stabilizes
TDP1 together with SUMOylation of TDP1. TDP1
PARylation enhances its recruitment to DNA
damage sites without interfering with TDP1 catalytic
activity. TDP1–PARP1 complexes, in turn recruit X-ray
repair cross-complementing protein 1 (XRCC1). This work identifies PARP1 as a key component driving
the repair of trapped Top1cc by TDP1.
 
Publisher Oxford University Press
 
Date 2014
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2049/1/NUCLEIC_ACIDS_RESEARCH__V_42_(_7_)_4435%2D4449;2014[36].pdf
Das, Benu Brata and Huang, Shar-yin N and Murai, Junko and Christophe , Ishita Rehman and Ame, Jean- and Sengupta, Souvik and Das, Subhendu K and Majumdar, Papiya and Zhang, Hongliang and Biard, Denis and Majumder, Hemanta K and Schreiber, Vale´ rie and Pommier, Yves (2014) PARP1–TDP1 coupling for the repair of topoisomerase I–induced DNA damage. Nucleic Acids Research, 42 (7). pp. 4435-4449.
 
Relation http://dx.doi.org/10.1093/nar/gku088
http://www.eprints.iicb.res.in/2049/