Journal of Biological Chemistry
Volume 284, Issue 35, 28 August 2009, Pages 23525-23531
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DNA: Replication, Repair, Recombination, and Chromosome Dynamics
hSSB1 and hSSB2 Form Similar Multiprotein Complexes That Participate in DNA Damage Response*

https://doi.org/10.1074/jbc.C109.039586Get rights and content
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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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This work was supported, in whole or in part, by National Institutes of Health Grant Z01: AG000657–09 from the Intramural Research Program of the National Institute on Aging and National Institutes of Health Grants CA123232 and CA129537 (to T. K. P.). This work was also supported by a grant from the National Health and Medical Research Council of Australia (to K. K. K.).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.