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Loss of RPA1 induces Chk2 phosphorylation through a caffeine‐sensitive pathway
Author(s) -
Araya Runa,
Hirai Itaru,
Meyerkord Cheryl L.,
Wang Hong-Gang
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.11.066
Subject(s) - phosphorylation , microbiology and biotechnology , gene knockdown , transfection , small interfering rna , downregulation and upregulation , dna damage , chemistry , biology , dna , apoptosis , biochemistry , gene
RPA is an important component of DNA replication, repair and recombination, but its involvement in the signaling of cell‐cycle checkpoints is not well understood. In this study, we show that knockdown of RPA1 by siRNA duplexes induces ATM (Ser1981) and Chk2 (Thr68), but not Chk1 (Ser345) phosphorylation and results in p21 upregulation in HeLa cells. However, the induction of Chk2 (Thr68) phosphorylation and p21 expression by RPA1 siRNA transfection can be completely blocked by the ATM inhibitor caffeine. Moreover, transfection of siRNAs targeting ATM dramatically reduces Chk2 (Thr68) phosphorylation in RPA1 knockdown cells. Taken together, these results suggest that loss of RPA1 activates the Chk2 signaling pathway in an ATM‐dependent manner.