Skip to content

Research at St Andrews

Single-stranded DNA-binding protein hSSB1 is critical for genomic stability

Research output: Contribution to journalArticle

DOI

Author(s)

D J Richard, E Bolderson, Liza Cubeddu, Ross Iain McAllister Wadsworth, K Savage, G G Sharma, M L Nicolette, S Tsvetanov, M J McIlwraith, R K Pandita, S Takeda, R T Hay, J Gautier, Stephen C. West, T T Paul, T K Pandita, Malcolm Frederick White, K K Khanna

School/Research organisations

Abstract

Single- strand DNA ( ssDNA)- binding proteins ( SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair(1). SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand- exchange proteins, activating transcription and mediating protein - protein interactions. In eukaryotes, the major SSB, replication protein A ( RPA), is a heterotrimer(1). Here we describe a second human SSB ( hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated ( ATM) kinase phosphorylates hSSB1 in response to DNA double- strand breaks ( DSBs). This phosphorylation event is required for DNA damage- induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell- cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S- phase cells and hSSB1 deficiency does not influence S- phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse end-points in the cellular DNA damage response.

Close

Details

Original languageEnglish
Pages (from-to)677-682
Number of pages6
JournalNature
Volume453
Issue number7195
DOIs
StatePublished - 29 May 2008

    Research areas

  • MAMMALIAN-CELLS, RAD52 PROTEIN, BREAK REPAIR, S-PHASE, DAMAGE, ATM, PHOSPHORYLATION, RECOMBINATION, ACTIVATION, CHECKPOINT

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Control of cyclic oligoadenylate synthesis in a type III CRISPR system

    Rouillon, C. M. J., Athukoralage, J. S., Graham, S., Gruschow, S. & White, M. F. 19 Jul 2018 In : eLife. 7, 22 p., e36734

    Research output: Contribution to journalArticle

  2. DNA repair in the Archaea – an emerging picture

    White, M. F. & Allers, T. 5 May 2018 In : FEMS Microbiology Reviews. Advance articles

    Research output: Contribution to journalReview article

  3. Prespacer processing and specific integration in a Type I-A CRISPR system

    Rollie, C., Graham, S., Rouillon, C. & White, M. F. 16 Feb 2018 In : Nucleic Acids Research. 46, 3, p. 1007-1020 14 p.

    Research output: Contribution to journalArticle

  4. DNA‐Interacting characteristics of the archaeal Rudiviral protein SIRV2_Gp1

    Peeters, E., Boon, M., Rollie, C. J. C., Willaert, R. G., Voet, M., White, M. F., Prangishvili, D., Lavigne, R. & Quax, T. E. F. Jul 2017 In : Viruses. 9, 7, 13 p., 190

    Research output: Contribution to journalArticle

  5. High-affinity RNA binding by a hyperthermophilic single-stranded DNA-binding protein

    Morten, M. J., Gamsjaeger, R., Cubeddu, L., Kariawasam, R., Peregrina, J. R., Penedo-Esteiro, J. C. & White, M. F. Mar 2017 In : Extremophiles. 21, 2, p. 369-379 11 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Nature (Journal)

    Dritschel, D. G. (Editor)
    2005 → …

    Activity: Publication peer-review and editorial workEditor of research journal

  2. Nature (Journal)

    Samuel, I. D. W. (Editor)
    2005 → …

    Activity: Publication peer-review and editorial workEditor of research journal

Related by journal

  1. An absolute sodium abundance for a cloud-free 'hot Saturn' exoplanet

    Nikolov, N. , Sing, D. K. , Fortney, J. J. , Goyal, J. M. , Drummond, B. , Evans, T. M. , Gibson, N. P. , De Mooj, E. J. W. , Rustamkulov, Z. , Wakeford, H. R. , Smalley, B. , Burgasser, A. J. , Hellier, C. , Helling, C. , Mayne, N. J. , Madhusudhan, N. , Kataria, T. , Baines, J. , Carter, A. L. , Ballester, G. E. & 3 others Barstow, J. K., McCleery, J. & Spake, J. J. 7 May 2018 In : Nature. 557, p. 526-529

    Research output: Contribution to journalArticle

  2. Inference of ecological and social drivers of human brain-size evolution

    Gonzalez Forero, M. & Gardner, A. 23 May 2018 In : Nature. 557, p. 554-557

    Research output: Contribution to journalLetter

  3. Age, extent and carbon storage of the central Congo Basin peatland complex

    Dargie, G. C., Lewis, S. L., Lawson, I. T., Mitchard, E. T. A., Page, S. E., Bocko, Y. E. & Ifo, S. A. 2 Feb 2017 In : Nature. 542, 7639, p. 86-90 5 p.

    Research output: Contribution to journalArticle

  4. Maximal Rashba-like spin splitting via kinetic energy-coupled inversion symmetry breaking

    Sunko, V., Rosner, H., Kushwaha, P., Khim, S., Mazzola, F., Bawden, L., Clark, O. J., Riley, J. M., Kasinathan, D., Haverkort, M. W., Kim, T. K., Hoesch, M., Fujii, J., Vobornik, I., Mackenzie, A. P. & King, P. D. 28 Sep 2017 In : Nature. 549, 7673, p. 492-496

    Research output: Contribution to journalArticle

ID: 424583