SWI/SNF factors required for cellular resistance to dna damage include arid1a and arid1b and show interdependent protein stability

Reiko Watanabe, Ayako Ui, Shin Ichiro Kanno, Hideaki Ogiwara, Takahiro Nagase, Takashi Kohno, Akira Yasui

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)


The SWI/SNF chromatin-remodeling family contains various protein complexes, which regulate gene expression during cellular development and influence DNA damage response in an ATP- and complex-dependent manner, of which details remain elusive. Recent human genome sequencing of various cancer cells revealed frequent mutations in SWI/SNF factors, especially ARID1A, a variant subunit in the BRG1-associated factor (BAF) complex of the SWI/SNF family. We combined live-cell analysis and gene-suppression experiments to show that suppression of either ARID1A or its paralog ARID1B led to reduced nonhomologous end joining activity of DNA double-strand breaks (DSB), decreased accumulation of KU70/KU80 proteins at DSB, and sensitivity to ionizing radiation, as well as to cisplatin and UV. Thus, in contrast to transcriptional regulation, both ARID1 proteins are required for cellular resistance to various types of DNA damage, including DSB. The suppression of other SWI/SNF factors, namely SNF5, BAF60a, BAF60c, BAF155, or BAF170, exhibits a similar phenotype. Of these factors, ARID1A, ARID1B, SNF5, and BAF60c are necessary for the immediate recruitment of the ATPase subunit of the SWI/SNF complex to DSB, arguing that both ARID1 proteins facilitate the damage response of the complex. Finally, we found interdependent protein stability among the SWI/SNF factors, suggesting their direct interaction within the complex and the reason why multiple factors are frequently lost in parallel in cancer cells. Taken together, we show that cancer cells lacking in the expression of certain SWI/SNF factors, including ARID1A, are deficient in DNA repair and potentially vulnerable to DNA damage.

Original languageEnglish
Pages (from-to)2465-2475
Number of pages11
JournalCancer Research
Issue number9
Publication statusPublished - 2014 Jan 5


Dive into the research topics of 'SWI/SNF factors required for cellular resistance to dna damage include arid1a and arid1b and show interdependent protein stability'. Together they form a unique fingerprint.

Cite this