Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation

Demuth, Ilja; Digweed, Martin; Concannon, Patrick

doi:10.1038/sj.onc.1207895

Cited by 75 publications

(105 citation statements)

References 47 publications

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“…Our own prior studies of hSNM1B have suggested a more general role for the protein in the cellular response to both DNA double-strand breaks or interstrand crosslinks [1]. In the current study, we extend these findings.…”

Section: Introductionsupporting

confidence: 79%

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Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation

et al. 2008

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Human SNM1B/Apollo is involved in the cellular response to DNA-damage, however, its precise role is unknown. Recent reports have implicated hSNM1B in the protection of telomeres. We have found hSNM1B to interact with TRF2, a protein which functions in telomere protection and in an early response to ionizing radiation. Here we show that endogenous hSNM1B forms foci which colocalize at telomeres with TRF1 and TRF2. However, we observed that additional hSNM1B foci could be induced upon exposure to ionizing radiation (IR). In live-cell-imaging experiments, hSNM1B localized to photoinduced double-strand breaks (DSBs) within 10s post-induction. Further supporting a role for hSNM1B in the early stages of the cellular response to DSBs, we observed that autophosphorylation of ATM, as well as the phosphorylation of ATM target proteins in response to IR, was attenuated in cells depleted of hSNM1B. These observations suggest an important role for hSNM1B in the response to IR damage, a role that may be, in part, upstream of the central player in maintenance of genome integrity, ATM.

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Section: Introductionsupporting

confidence: 79%

“…We have recently described hSNM1B as a new gene involved in this cellular response to DNA damage [1]. The hSNM1B protein belongs to the SNM1-family.…”

Section: Introductionmentioning

confidence: 99%

Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation

et al. 2008

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“…RSBN1 is expressed exclusively in germ cells (45). DCLRE1B is expressed ubiquitously, but its function in the cellular response to DNA intrastrand cross-links does not suggest a role in immune responses (46). On the other hand, C1orf178 is a member of the Bcl-2 family with some proapoptotic function and is expressed in both spleen and thymus (42).…”

Section: Discussionmentioning

confidence: 99%

A Haplotype-Based Analysis of the PTPN22 Locus in Type 1 Diabetes

Önengüt-Gümüşcü

Buckner²,

Concannon

2006

Diabetes

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A recent addition to the list of widely confirmed type 1 diabetes risk loci is the PTPN22 gene encoding a lymphoidspecific phosphatase (Lyp). However, evidence supporting a role for PTPN22 in type 1 diabetes derives entirely from the study of just one coding single nucleotide polymorphism, 1858C/T. In the current study, the haplotype structure of the PTPN22 region was determined, and individual haplotypes were tested for association with type 1 diabetes in family-based tests. The 1858T risk allele occurred on only a single haplotype that was strongly associated with type 1 diabetes (P ‫؍‬ 7.9 ؋ 10 ؊5 ). After controlling for the effects of this allele, two other haplotypes were observed to be weakly associated with type 1 diabetes (P < 0.05). Sequencing of the coding region of PTPN22 on these haplotypes revealed a novel variant (2250G/C) predicted to result in a nonsynonymous amino acid substitution. Analysis of PTPN22 transcripts from a subject heterozygous for this variant indicated that it interfered with normal mRNA splicing, resulting in a premature termination codon after exon 17. These results support the conclusion that the 1858C/T allele is the major risk variant for type 1 diabetes in the PTPN22 locus, but they suggest that additional infrequent coding variants at PTPN22 may also contribute to type 1 diabetes risk.

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confidence: 99%

“…Knock-out of Snm1B in chicken cells and small interfering RNA against Snm1B in human cells both result in mild sensitivity to interstrand cross-linking agents (28,29). Knockdown of Snm1B by small interfering RNA induces an increase in aberrant metaphase morphology in human cells (29).The importance of Artemis on telomere stability and telomere length regulation led us to examine whether the other two DNA-binding members of the ␤-CASP family, human (h) 2 Snm1A and hSnm1B associate with telomeres. …”

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confidence: 99%

hSnm1B Is a Novel Telomere-associated Protein

Freibaum

Counter

2006

Journal of Biological Chemistry

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Artemis, a member of the ␤-CASP family, has been implicated in the regulation of both telomere stability and length. Prompted by this, we examined whether the other two putative DNA-binding members of this family, hSnm1A and hSnm1B, may associate with telomeres. hSnm1A was found to not interact with the telomere. Conversely, hSnm1B was found to associate with telomeres in vivo by both immunofluorescence and chromatin immunoprecipitation. Furthermore, the C terminus of hSnm1B was shown to interact with the TRF homology domain of TRF2 indicating that hSnm1B is likely recruited to the telomere via interaction with the doublestranded telomere-binding protein TRF2.The ends of human chromosomes are capped and protected by a DNAprotein structure termed the telomere. The DNA portion of human telomeres is composed of a G-rich repeat (TTAGGG) that extends past the complementary C-rich strand, forming a 3Ј extension. This extension has been found by electron microscopy to loop back and invade the double-stranded region, forming a large loop structure termed the t-loop (1). The protein portion of telomeres is composed of a core of six proteins termed the telosome or shelterin (2-4), three of which directly bind telomeric DNA, TRF1 (5), TRF2 (6, 7), and hPot1 (8), and three that associate with the DNA-binding proteins, Tin2 (9), Tpp1 (10 -12), and Rap1 (13). TRF1 and TRF2 bind double-stranded telomeric DNA (7), whereas hPot1 binds the single-stranded region of the telomere (8). In addition to this core complex, many other proteins are known to associate and function at the telomere, albeit at a smaller concentration and often indirectly through binding to TRF1 or TRF2 (4).One protein that influences the stability of the telomere but is not a member of the described core telomeric complex is Artemis. This protein is a member of the ␤-CASP family of proteins that contain a unique metallo-␤-lactamase domain that hydrolyzes nucleic acids (14). Artemis is well established to play a role in non-homologous recombination where it forms a complex with DNA-PK CS , which cleaves the intermediate hairpin loop structure formed during V(D)J recombination and non-homologous end joining (15). However, Artemis-deficient mice have increased telomeric fusions, suggesting that this family of proteins plays a role in telomere structure or function (16). Indeed, Artemis deficient cell lines have increased rates of telomeric shortening as well as rapid accumulation of anaphase bridges (17).Five mammalian proteins belonging to the ␤-CASP family have been identified, two of which hydrolyze RNA (18 -21), whereas the remaining three, Artemis, Snm1A, and Snm1B, are believed to function solely on DNA substrates (22). Snm1A localizes to DNA double-strand breaks after ionizing radiation; although cells lacking Snm1A are sensitive only to mitomycin C and not ionizing radiation (23,24). Snm1A co-localizes with the DNA damage response protein 53BP before and after exposure to ionizing radiation (23). Snm1A is also highly up-regulated during mitosis and is be...

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Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation

Cited by 75 publications

References 47 publications

Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation

Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation

A Haplotype-Based Analysis of the PTPN22 Locus in Type 1 Diabetes

hSnm1B Is a Novel Telomere-associated Protein

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