hSSB1 and hSSB2 form similar multiprotein complexes that participate in DNA damage response

Li, Yongjian, Bolderson, Emma, Kumar, Rakesh, Muniandy, Parameswary, Xue, Yutong, Richard, Derek, Seidman, Michael, Pandita, Tej, Khanna, Kum, & Wang, Weidong (2009) hSSB1 and hSSB2 form similar multiprotein complexes that participate in DNA damage response. Journal of Biological Chemistry, 284(35), pp. 23525-23531.

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Abstract

hSSB1 (human single strand DNA-binding protein 1) has been shown to participate in homologous recombination (HR)-dependent repair of DNA double strand breaks (DSBs) and ataxia telangiectasia-mutated (ATM)-mediated checkpoint pathways. Here we present evidence that hSSB2, a homolog of hSSB1, plays a role similar to hSSB1 in DNA damage-response pathways. This was evidenced by findings that hSSB2-depleted cells resemble hSSB1-depleted cells in hypersensitivity to DNA-damaging reagents, reduced efficiency in HR-dependent repair of DSBs, and defective ATM-dependent phosphorylation. Notably, hSSB1 and hSSB2 form separate complexes with two identical proteins, INTS3 and hSSBIP1 (C9ORF80). Cells depleted of INTS3 and hSSBIP1 also exhibited hypersensitivity to DNA damage reagents, chromosomal instability, and reduced ATM-dependent phosphorylation. hSSBIP1 was rapidly recruited to laser-induced DSBs, a feature also similar to that reported for hSSB1. Depletion of INTS3 decreased the stability of hSSB1 and hSSBIP1, suggesting that INTS3 may provide a scaffold to allow proper assembly of the hSSB complexes. Thus, our data demonstrate that hSSB1 and hSSB2 form two separate complexes with similar structures, and both are required for efficient HR-dependent repair of DSBs and ATM-dependent signaling pathways.

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59 citations in Scopus
55 citations in Web of Science®
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ID Code: 44674
Item Type: Journal Article
Refereed: Yes
Additional Information: This research was originally published in the Journal of Biological Chemistry. Yongjiang Li, Emma Bolderson, Rakesh Kumar, Parameswary A. Muniandy, Yutong Xue, Derek J. Richard, Michael Seidman, Tej K. Pandita, Kum Kum Khanna and Weidong Wang. hSSB1 and hSSB2 Form Similar Multiprotein Complexes That Participate in DNA Damage Response. Journal of Biological Chemistry. 2009; 284: 23525-23531. © the American Society for Biochemistry and Molecular Biology.
DOI: 10.1074/jbc.C109.039586
ISSN: 0021-9258
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)
Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > CHEMICAL ENGINEERING (090400)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 24 Aug 2011 22:13
Last Modified: 19 May 2017 01:14

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