TY - JOUR
T1 - Translocation of XRCC1 and DNA ligase IIIα from centrosomes to chromosomes in response to DNA damage in mitotic human cells
AU - Okano, Satoshi
AU - Lan, Li
AU - Tomkinson, Alan E.
AU - Yasui, Akira
N1 - Funding Information:
This work was supported in part by Grant-in-Aid for Scientific Research (nos 12143201 and 13480162) from the Ministry of Education, Science, Sports and Culture of Japan, by the Fund for ‘Studies on the Molecular Biological Basis for Low-Dose Radiation Effects’ from the Japan Atomic Energy Research Institute through a contract with the Nuclear Safety ResearchAssociationtoA.Y.andbyagrant(ES12512)toA.E.T. from the United States Public Health Service. Funding to pay the Open Access publication charges for this article was provided by Japan Society for the Promotion of Science.
PY - 2005
Y1 - 2005
N2 - DNA single-strand breaks (SSBs) are the most frequent lesions caused by oxidative DNA damage. They disrupt DNA replication, give rise to double-strand breaks and lead to cell death and genomic instability. It has been shown that the XRCC1 protein plays a key role in SSBs repair. We have recently shown in living human cells that XRCC1 accumulates at SSBs in a fully poly(ADP-ribose) (PAR) synthesis-dependent manner and that the accumulation of XRCC1 at SSBs is essential for further repair processes. Here, we show that XRCC1 and Its partner protein, DNA ligase IIIα, localize at the centrosomes and their vicinity in metaphase cells and disappear during anaphase. Although the function of these proteins in centrosomes during metaphase is unknown, this centrosomal localization is PAR-dependent, because neither of the proteins is observed in the centrosomes in the presence of PAR polymerase inhibitors. On treatment of metaphase cells with H2O2, XRCC1 and DNA ligase IIIα translocate immediately from the centrosomes to mitotic chromosomes. These results show for the first time that the repair of SSBs is present in the early mitotic chromosomes and that there is a dynamic response of XRCC1 and DNA ligase IIIα to SSBs, in which these proteins are recruited from the centrosomes, where metaphase-dependent activation of PAR polymerase occurs, to mitotic chromosomes, by SSBs-dependent activation of PAR polymerase.
AB - DNA single-strand breaks (SSBs) are the most frequent lesions caused by oxidative DNA damage. They disrupt DNA replication, give rise to double-strand breaks and lead to cell death and genomic instability. It has been shown that the XRCC1 protein plays a key role in SSBs repair. We have recently shown in living human cells that XRCC1 accumulates at SSBs in a fully poly(ADP-ribose) (PAR) synthesis-dependent manner and that the accumulation of XRCC1 at SSBs is essential for further repair processes. Here, we show that XRCC1 and Its partner protein, DNA ligase IIIα, localize at the centrosomes and their vicinity in metaphase cells and disappear during anaphase. Although the function of these proteins in centrosomes during metaphase is unknown, this centrosomal localization is PAR-dependent, because neither of the proteins is observed in the centrosomes in the presence of PAR polymerase inhibitors. On treatment of metaphase cells with H2O2, XRCC1 and DNA ligase IIIα translocate immediately from the centrosomes to mitotic chromosomes. These results show for the first time that the repair of SSBs is present in the early mitotic chromosomes and that there is a dynamic response of XRCC1 and DNA ligase IIIα to SSBs, in which these proteins are recruited from the centrosomes, where metaphase-dependent activation of PAR polymerase occurs, to mitotic chromosomes, by SSBs-dependent activation of PAR polymerase.
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U2 - 10.1093/nar/gki190
DO - 10.1093/nar/gki190
M3 - Article
C2 - 15653642
AN - SCOPUS:13744257257
VL - 33
SP - 422
EP - 429
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 1
ER -