Abstract
Maintenance of genome integrity is crucial for the survival of an organism. Increasing evidence suggests that defective DNA damage response promotes genome instability and accelerates age-related degeneration. The RecQ family of DNA helicases plays important roles in DNA replication and the DNA damage response. There are five human RecQ helicases, amongst which mutations in BLM, WRN, and RECQ4 have been linked to human diseases displaying symptoms of accelerated aging to various degrees. Recent studies have provided new insights into the mechanisms that control early stages of the DNA damage response, and shed light on common roles of the RecQ helicases in DNA replication and the DNA damage response. Here, we review the evidence for defective DNA damage response being a feature linking mutations in RecQ helicases to premature aging diseases. Data are accumulating to suggest that RecQ helicases impart signaling and repair functions in the response to DNA damage.
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Ababou, M., Dumaire, V., Lecluse, Y., and mor-Gueret, M. (2002). Bloom’s syndrome protein response to ultraviolet-C radiation and hydroxyurea-mediated DNA synthesis inhibition. Oncogene 21, 2079–2088.
Adams, M.D., McVey, M., and Sekelsky, J.J. (2003). Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing. Science 299, 265–267.
Bachrati, C.Z. and Hickson, I.D. (2008). RecQ helicases: guardian angels of the DNA replication fork. Chromosoma 117, 219–233.
Bakkenist, C.J. and Kastan, M.B. (2003). DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421, 499–506.
Beall, E.L. and Rio, D.C. (1996). Drosophila IRBP/Ku p70 corresponds to the mutagen-sensitive mus309 gene and is involved in P-element excision in vivo. Genes Dev. 10, 921–933.
Berkovich, E., Monnat, R.J., Jr., and Kastan, M.B. (2007). Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat. Cell Biol. 9, 683–690.
Bohr, V.A., Souza, P.N., Nyaga, S.G., Dianov, G., Kraemer, K., Seidman, M.M., and Brosh, R.M., Jr. (2001). DNA repair and mutagenesis in Werner syndrome. Environ. Mol. Mutagen. 38, 227–234.
Botuyan, MV., Lee, J., Ward, IM., Kim, JE., Thompson, JR., Chen, J., and Mer, G. (2006). Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127, 1361–1373.
Brown, E.J. and Baltimore, D. (2000). ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 14, 397–402.
Bugreev, D.V., Brosh, R.M., Jr., and Mazin, A.V. (2008). RECQ1 possesses DNA branch migration activity. J. Biol. Chem. 283, 20231–20242.
Campisi, J. (2005). Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513–522.
Chang, S., Multani, A.S., Cabrera, N.G., Naylor, M.L., Laud, P., Lombard, D., Pathak, S., Guarente, L., and DePinho, R.A. (2004). Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat. Genet. 36, 877–882.
Chen, C.C., Carson, J.J., Feser, J., Tamburini, B., Zabaronick, S., Linger, J., and Tyler, J.K. (2008). Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair. Cell 134, 231–243.
Cheng, W.H., Muftic, D., Muftuoglu, M., Dawut, L., Morris, C., Helleday, T., Shiloh, Y., and Bohr, V.A. (2008). WRN is required for ATM activation and the S-phase checkpoint in response to interstrand crosslink-induced DNA double strand breaks. Mol. Biol. Cell 19, 3923–3933.
Cheng, W.H., Sakamoto, S., Fox, J.T., Komatsu, K., Carney, J., and Bohr, V.A. (2005). Werner syndrome protein associates with gamma H2AX in a manner that depends upon Nbs1. FEBS Lett. 579, 1350–1356.
Cheng, W.H., von Kobbe, K.C., Opresko, P.L., Arthur, L.M., Komatsu, K., Seidman, M.M., Carney, J.P., and Bohr, V.A. (2004). Linkage between Werner syndrome protein and the Mre11 complex via Nbs1. J. Biol. Chem. 279, 21169–21176.
Chester, N., Babbe, H., Pinkas, J., Manning, C., and Leder, P. (2006). Mutation of the murine Bloom’s syndrome gene produces global genome destabilization. Mol. Cell Biol. 26, 6713–6726.
Chester, N., Kuo, F., Kozak, C., O’Hara, C.D., and Leder, P. (1998). Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom’s syndrome gene. Genes Dev. 12, 3382–3393.
Choudhary, S., Doherty, K.M., Handy, C.J., Sayer, J.M., Yagi, H., Jerina, D.M., and Brosh, R.M., Jr. (2006). Inhibition of Werner syndrome helicase activity by benzo[a]pyrene diol epoxide adducts can be overcome by replication protein A. J. Biol. Chem. 281, 6000–6009.
Chun, H.H. and Gatti, R.A. (2004). Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst) 3, 1187–1196.
Cimprich, K.A. and Cortez, D. (2008). ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 9, 616–627.
Compton, S.A., Tolun, G., Kamath-Loeb, A.S., Loeb, L.A., and Griffith, J.D. (2008). The Werner syndrome protein binds replication fork and holliday junction DNAs as an oligomer. J. Biol. Chem. 283, 24478–24483.
Constantinou, A., Tarsounas, M., Karow, J.K., Brosh, R.M., Bohr, V.A., Hickson, I.D., and West, S.C. (2000). Werner’s syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest. EMBO Rep. 1, 80–84.
Crabbe, L., Jauch, A., Naeger, C.M., Holtgreve-Grez, H., and Karlseder, J. (2007). Telomere dysfunction as a cause of genomic instability in Werner syndrome. Proc. Natl. Acad. Sci. U.S.A. 104, 2205–2210.
Crabbe, L., Verdun, R.E., Haggblom, C.I., and Karlseder, J. (2004). Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306, 1951–1953.
Cuadrado, M., Martinez-Pastor, B., Murga, M., Toledo, L.I., Gutierrez-Martinez,P., Lopez, E., and Fernandez-Capetillo, O. (2006). ATM regulates ATR chromatin loading in response to DNA double-strand breaks. J. Exp. Med. 203, 297–303.
D’Amours, D. and Jackson, S.P. (2002). The Mre11 complex: at the crossroads of dna repair and checkpoint signalling. Nat. Rev. Mol. Cell Biol. 3, 317–327.
Davies, S.L., North, P.S., and Hickson, I.D. (2007). Role for BLM in replication-fork restart and suppression of origin firing after replicative stress. Nat. Struct. Mol. Biol. 14, 677–679.
d’Adda di Fagagna, F., Teo, S.H., and Jackson, S.P. (2004). Functional links between telomeres and proteins of the DNA-damage response. Genes Dev. 18, 1781–1799.
De Klein, A., Muijtjens, M., van Os, R., Verhoeven, Y., Smit, B., Carr, A.M., Lehmann, A.R., and Hoeijmakers, J.H. (2000). Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr. Biol. 10, 479–482.
Du, X., Shen, J., Kugan, N., Furth, E.E., Lombard, D.B., Cheung, C., Pak, S., Luo, G., Pignolo, R.J., DePinho, R.A., Guarente, L., and Johnson, F.B. (2004). Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol. Cell Biol. 24, 8437–8446.
Falck, J., Coates, J., and Jackson, S.P. (2005). Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434, 605–611.
Fan, W. and Luo, J. (2008). RecQ4 facilitates UV-induced DNA damage repair through interaction with nucleotide excision repair factor XPA. J. Biol. Chem 283, 29037–29044.
Frei, C. and Gasser, S.M. (2000). The yeast Sgs1p helicase acts upstream of Rad53p in the DNA replication checkpoint and colocalizes with Rad53p in S-phase-specific foci. Genes Dev. 14, 81–96.
Froget, B., Blaisonneau, J., Lambert, S., and Baldacci, G. (2008). Cleavage of stalled forks by fission yeast mus81/eme1 in absence of DNA replication checkpoint. Mol. Biol. Cell 19, 445–456.
Gaymes, T.J., North, P.S., Brady, N., Hickson, I.D., Mufti, G.J., and Rassool, F.V. (2002). Increased error-prone non homologous DNA end-joining – a proposed mechanism of chromosomal instability in Bloom’s syndrome. Oncogene 21, 2525–2533.
Gilson, E. and Geli, V. (2007). How telomeres are replicated. Nat. Rev. Mol. Cell Biol. 8, 825–838.
Goldberg, M., Stucki, M., Falck, J., D’Amours, D., Rahman, D., Pappin, D., Bartek, J., and Jackson, S.P. (2003). MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421, 952–956.
Goodarzi, A.A., Noon, A.T., Deckbar, D., Ziv, Y., Shiloh, Y., Lobrich, M., and Jeggo, P.A. (2008). ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol. Cell 31, 167–177.
Grabowski, M.M., Svrzikapa, N., and Tissenbaum, H.A. (2005). Bloom syndrome ortholog HIM-6 maintains genomic stability in C. elegans. Mech. Ageing Dev. 126, 1314–1321.
Gray, M.D., Shen, J.C., Kamath-Loeb, A.S., Blank, A., Sopher, B.L., Martin, G.M., Oshima, J., and Loeb, L.A. (1997). The Werner syndrome protein is a DNA helicase. Nat. Genet. 17, 100–103.
Hayflick, L. (1965). The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37, 614–636.
Hickson, I.D. (2003). RecQ helicases: caretakers of the genome. Nat. Rev. Cancer 3, 169–178.
Hishida, T., Han, Y.W., Shibata, T., Kubota, Y., Ishino, Y., Iwasaki, H., and Shinagawa, H. (2004). Role of the Escherichia coli RecQ DNA helicase in SOS signaling and genome stabilization at stalled replication forks. Genes Dev. 18, 1886–1897.
Hoki, Y., Araki, R., Fujimori, A., Ohhata, T., Koseki, H., Fukumura, R., Nakamura, M., Takahashi, H., Noda, Y., Kito, S., and Abe, M. (2003). Growth retardation and skin abnormalities of the Recql4-deficient mouse. Hum. Mol. Genet. 12, 2293–2299.
Hu, Y., Lu, X., Barnes, E., Yan, M., Lou, H., and Luo, G. (2005). Recql5 and Blm RecQ DNA helicases have nonredundant roles in suppressing crossovers. Mol. Cell Biol. 25, 3431–3442.
Hu, Y., Raynard, S., Sehorn, M.G., Lu, X., Bussen, W., Zheng, L., Stark, J.M., Barnes, E.L., Chi, P., Janscak, P., Jasin, M., Vogel, H., Sung, P., and Luo, G. (2007). RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes Dev. 21, 3073–3084.
Huang, S., Li, B., Gray, M.D., Oshima, J., Mian, I.S., and Campisi, J. (1998). The premature ageing syndrome protein, WRN, is a 3′ ➔5′ exonuclease. Nat. Genet. 20, 114–116.
Huyen, Y., Zgheib, O., Ditullio, R.A., Jr., Gorgoulis, V.G., Zacharatos, P., Petty, T.J., Sheston, E.A., Mellert, H.S., Stavridi, E.S., and Halazonetis, T.D. (2004). Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432, 406–411.
Hyun, M., Bohr, V.A., and Ahn, B. (2008). Biochemical characterization of the WRN-1 RecQ helicase of Caenorhabditis elegans. Biochemistry 47, 7583–7593.
Jacobs, J.J. and de, L.T. (2004). Significant role for p16INK4a in p53-independent telomere-directed senescence. Curr. Biol. 14, 2302–2308.
Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G.C., Lukas, J., and Jackson, S.P. (2006). ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat. Cell Biol. 8, 37–45.
Jeong, Y.S., Kang, Y., Lim, K.H., Lee, M.H., Lee, J., and Koo, H.S. (2003). Deficiency of Caenorhabditis elegans RecQ5 homologue reduces life span and increases sensitivity to ionizing radiation. DNA Repair (Amst) 2, 1309–1319.
Kanagaraj, R., Saydam, N., Garcia, P.L., Zheng, L., and Janscak, P. (2006). Human RECQ5beta helicase promotes strand exchange on synthetic DNA structures resembling a stalled replication fork. Nucleic Acids Res. 34, 5217–5231.
Karmakar, P., Seki, M., Kanamori, M., Hashiguchi, K., Ohtsuki, M., Murata, E., Inoue, E., Tada, S., Lan, L., Yasui, A., and Enomoto, T. (2006). BLM is an early responder to DNA double-strand breaks. Biochem. Biophys. Res. Commun. 348, 62–69.
Keogh, M.C., Kim, J.A., Downey, M., Fillingham, J., Chowdhury, D., Harrison, J.C., Onishi, M., Datta, N., Galicia, S., Emili, A., Lieberman, J., Shen, X., Buratowski, S., Haber, J.E., Durocher, D., Greenblatt, J.F., and Krogan, N.J. (2006). A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature 439, 497–501.
Kitao, S., Shimamoto, A., Goto, M., Miller, R.W., Smithson, W.A., Lindor, N.M., and Furuichi, Y. (1999). Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome.Nat. Genet. 22, 82–84.
Kozlov, S.V., Graham, M.E., Peng, C., Chen, P., Robinson, P.J., and Lavin, M.F. (2006). Involvement of novel autophosphorylation sites in ATM activation. EMBO J. 25, 3504–3514.
Kubota, Y., Takase, Y., Komori, Y., Hashimoto, Y., Arata, T., Kamimura, Y., Araki, H., and Takisawa, H. (2003). A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication. Genes Dev. 17, 1141–1152.
Kyng, K.J., May, A., Kolvraa, S., and Bohr, V.A. (2003). Gene expression profiling in Werner syndrome closely resembles that of normal aging. Proc. Natl. Acad. Sci. U.S.A. 100, 12259–12264.
Lan, L., Nakajima, S., Komatsu, K., Nussenzweig, A., Shimamoto, A., Oshima, J., and Yasui, A. (2005). Accumulation of Werner protein at DNA double-strand breaks in human cells. J. Cell Sci. 118, 4153–4162.
Laud, P.R., Multani, A.S., Bailey, S.M., Wu, L., Ma, J., Kingsley, C., Lebel, M., Pathak, S., DePinho, R.A., and Chang, S. (2005). Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes Dev. 19, 2560–2570.
Lee, J.H. and Paull, T.T. (2007). Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene 26, 7741–7748.
Lee, J.H. and Paull, T.T. (2005). ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308, 551–554.
Lee, S.J., Yook, J.S., Han, S.M., and Koo, H.S. (2004). A Werner syndrome protein homolog affects C. elegans development, growth rate, life span and sensitivity to DNA damage by acting at a DNA damage checkpoint. Development 131, 2565–2575.
LeRoy, G., Carroll, R., Kyin, S., Seki, M., and Cole, M.D. (2005). Identification of RecQL1 as a Holliday junction processing enzyme in human cell lines. Nucleic Acids Res. 33, 6251–6257.
Liberi, G., Maffioletti, G., Lucca, C., Chiolo, I., Baryshnikova, A., Cotta-Ramusino, C., Lopes, M., Pellicioli, A., Haber, J.E., and Foiani, M. (2005). Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase. Genes Dev. 19, 339–350.
Lou, Z., Minter-Dykhouse, K., Franco, S., Gostissa, M., Rivera, M.A., Celeste, A., Manis, J.P., van, D.J., Nussenzweig, A., Paull, T.T., Alt, F.W., and Chen, J. (2006). MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol. Cell 21, 187–200.
Machwe, A., Xiao, L., Groden, J., and Orren, D.K. (2006). The Werner and Bloom syndrome proteins catalyze regression of a model replication fork. Biochemistry 45, 13939–13946.
Macris, M.A., Krejci, L., Bussen, W., Shimamoto, A., and Sung, P. (2006). Biochemical characterization of the RECQ4 protein, mutated in Rothmund-Thomson syndrome. DNA Repair (Amst) 5, 172–180.
Matsuno, K., Kumano, M., Kubota, Y., Hashimoto, Y., and Takisawa, H. (2006). The N-terminal noncatalytic region of Xenopus RecQ4 is required for chromatin binding of DNA polymerase alpha in the initiation of DNA replication. Mol. Cell Biol. 26, 4843–4852.
McVey, M., Andersen, S.L., Broze, Y., and Sekelsky, J. (2007). Multiple functions of Drosophila BLM helicase in maintenance of genome stability. Genetics 176, 1979–1992.
McVey, M., Larocque, J.R., Adams, M.D., and Sekelsky, J.J. (2004). Formation of deletions during double-strand break repair in Drosophila DmBlm mutants occurs after strand invasion. Proc. Natl. Acad. Sci. U.S.A. 101, 15694–15699.
O’Driscoll, M. and Jeggo, P.A. (2006). The role of double-strand break repair – insights from human genetics. Nat. Rev. Genet. 7, 45–54.
Onclercq-Delic, R., Calsou, P., Delteil, C., Salles, B., Papadopoulo, D., and mor-Gueret, M. (2003). Possible anti-recombinogenic role of Bloom’s syndrome helicase in double-strand break processing. Nucleic Acids Res. 31, 6272–6282.
Ozsoy, A.Z., Ragonese, H.M., and Matson, S.W. (2003). Analysis of helicase activity and substrate specificity of Drosophila RECQ5. Nucleic Acids Res. 31, 1554–1564.
Petermann, E. and Caldecott, K.W. (2006). Evidence that the ATR/Chk1 pathway maintains normal replication fork progression during unperturbed S phase. Cell Cycle 5, 2203–2209.
Petkovic, M., Dietschy, T., Freire, R., Jiao, R., and Stagljar, I. (2005). The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability. J. Cell Sci. 118, 4261–4269.
Pichierri, P., Franchitto, A., and Rosselli, F. (2004). BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks. EMBO J. 23, 3154–3163.
Pirzio, L.M., Pichierri, P., Bignami, M., and Franchitto, A. (2008). Werner syndrome helicase activity is essential in maintaining fragile site stability. J. Cell Biol. 180, 305–314.
Poot, M., Gollahon, K.A., Emond, M.J., Silber, J.R., and Rabinovitch, P.S. (2002). Werner syndrome diploid fibroblasts are sensitive to 4-nitroquinoline-N-oxide and 8-methoxypsoralen: implications for the disease phenotype. FASEB J. 16, 757–758.
Poot, M., Hoehn, H., Runger, T.M., and Martin, G.M. (1992). Impaired S-phase transit of Werner syndrome cells expressed in lymphoblastoid cell lines. Exp. Cell Res. 202, 267–273.
Poot, M., Yom, J.S., Whang, S.H., Kato, J.T., Gollahon, K.A., and Rabinovitch, P.S. (2001). Werner syndrome cells are sensitive to DNA cross-linking drugs. FASEB J. 15, 1224–1226.
Ralf, C., Hickson, I.D., and Wu, L. (2006). The Bloom’s syndrome helicase can promote the regression of a model replication fork. J. Biol. Chem. 281, 22839–22846.
Rothfuss, A. and Grompe, M. (2004). Repair kinetics of genomic interstrand DNA cross-links: evidence for DNA double-strand break-dependent activation of the Fanconi anemia/BRCA pathway. Mol. Cell Biol. 24, 123–134.
Rouse, J. and Jackson, S.P. (2002). Interfaces between the detection, signaling, and repair of DNA damage. Science 297, 547–551.
Ruzankina, Y., Pinzon-Guzman, C., Asare, A., Ong, T., Pontano, L., Cotsarelis, G., Zediak, V.P., Velez, M., Bhandoola, A., and Brown, E.J. (2007). Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 1, 113–126.
Saintigny, Y., Makienko, K., Swanson, C., Emond, M.J., and Monnat, R.J., Jr. (2002). Homologous recombination resolution defect in werner syndrome. Mol. Cell Biol. 22, 6971–6978.
Sangrithi, M.N., Bernal, J.A., Madine, M., Philpott, A., Lee, J., Dunphy, W.G., and Venkitaraman, A.R. (2005). Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome. Cell 121, 887–898.
Saunders, R.D., Boubriak, I., Clancy, D.J., and Cox, L.S. (2008). Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity. Aging Cell 7, 418–425.
Schultz, L.B., Chehab, N.H., Malikzay, A., and Halazonetis, T.D. (2000). p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. J. Cell Biol. 151, 1381–1390.
Sekelsky, J.J., Brodsky, M.H., Rubin, G.M., and Hawley, R.S. (1999). Drosophila and human RecQ5 exist in different isoforms generated by alternative splicing. Nucleic Acids Res. 27, 3762–3769.
Sengupta, S., Robles, A.I., Linke, S.P., Sinogeeva, N.I., Zhang, R., Pedeux, R., Ward, I.M., Celeste, A., Nussenzweig, A., Chen, J., Halazonetis, T.D., and Harris, C.C. (2004). Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J. Cell Biol. 166, 801–813.
Sharma, S. and Brosh, R.M., Jr. (2007). Human RECQ1 is a DNA damage responsive protein required for genotoxic stress resistance and suppression of sister chromatid exchanges. PLoS. ONE. 2, e1297.
Sharma, S. and Brosh, R.M., Jr. (2008). Unique and important consequences of RECQ1 deficiency in mammalian cells. Cell Cycle 7, 989–1000.
Shiloh, Y. (2006). The ATM-mediated DNA-damage response: taking shape. Trends Biochem. Sci. 31, 402–410.
Shimura, T., Torres, M.J., Martin, M.M., Rao, V.A., Pommier, Y., Katsura, M., Miyagawa, K., and Aladjem, M.I. (2008). Bloom’s syndrome helicase and Mus81 are required to induce transient double-strand DNA breaks in response to DNA replication stress. J. Mol. Biol. 375, 1152–1164.
Sidorova, J.M., Li, N., Folch, A., and Monnat, R.J., Jr. (2008). The RecQ helicase WRN is required for normal replication fork progression after DNA damage or replication fork arrest. Cell Cycle 7, 796–807.
So, S., Adachi, N., Lieber, M.R., and Koyama, H. (2004). Genetic interactions between BLM and DNA ligase IV in human cells. J. Biol. Chem. 279, 55433–55442.
Stewart, E., Chapman, C.R., Al-Khodairy, F., Carr, A.M., and Enoch, T. (1997). rqh1+, a fission yeast gene related to the Bloom’s and Werner’s syndrome genes, is required for reversible S phase arrest. EMBO J. 16, 2682–2692.
Stiff, T., Reis, C., Alderton, G.K., Woodbine, L., O’Driscoll, M., and Jeggo, P.A. (2005). Nbs1 is required for ATR-dependent phosphorylation events. EMBO J. 24, 199–208.
Stiff, T., Walker, S.A., Cerosaletti, K., Goodarzi, A.A., Petermann, E., Concannon, P., O’Driscoll, M., and Jeggo, P.A. (2006). ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO J. 25, 5775–5782.
Stucki, M., Clapperton, J.A., Mohammad, D., Yaffe, M.B., Smerdon, S.J., and Jackson, S.P. (2005). MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123, 1213–1226.
Sun, Y., Jiang, X., Chen, S., Fernandes, N., and Price, B.D. (2005). A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc. Natl. Acad. Sci. U.S.A. 102, 13182–13287.
Takeuchi, F., Hanaoka, F., Goto, M., Akaoka, I., ori, T., Yamada, M., and Miyamoto, T. (1982). Altered frequency of initiation sites of DNA replication in Werner’s syndrome cells. Hum. Genet. 60, 365–368.
Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., and Shiloh, Y. (2003). Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 22, 5612–5621.
Verdun, R.E., Crabbe, L., Haggblom, C., and Karlseder, J. (2005). Functional human telomeres are recognized as DNA damage in G2 of the cell cycle. Mol. Cell 20, 551–561.
Verdun, R.E. and Karlseder, J. (2007). Replication and protection of telomeres. Nature 447, 924–931.
von Kobbe, K.C., Thoma, N.H., Czyzewski, B.K., Pavletich, N.P., and Bohr, V.A. (2003). Werner syndrome protein contains three structure-specific DNA binding domains. J. Biol. Chem. 278, 52997–53006.
Wicky, C., Alpi, A., Passannante, M., Rose, A., Gartner, A., and Muller, F. (2004). Multiple genetic pathways involving the Caenorhabditis elegans Bloom’s syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stability in the germ line. Mol. Cell Biol. 24, 5016–5027.
Wright, W.E. and Shay, J.W. (1992). The two-stage mechanism controlling cellular senescence and immortalization. Exp. Gerontol. 27, 383–389.
Wu, L. and Hickson, I.D. (2003). The Bloom’s syndrome helicase suppresses crossing over during homologous recombination. Nature 426, 870–874.
Wyllie, F.S., Jones, C.J., Skinner, J.W., Haughton, M.F., Wallis, C., Wynford-Thomas, D., Faragher, R.G., and Kipling, D. (2000). Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts. Nat. Genet. 24, 16–17.
Yu, C.E., Oshima, J., Fu, Y.H., Wijsman, E.M., Hisama, F., Alisch, R., Matthews, S., Nakura, J., Miki, T., Ouais, S., Martin, G.M., Mulligan, J., and Schellenberg, G.D. (1996). Positional cloning of the Werner’s syndrome gene. Science 272, 258–262.
Ziv, Y., Bielopolski, D., Galanty, Y., Lukas, C., Taya, Y., Schultz, D.C., Lukas, J., Bekker-Jensen, S., Bartek, J., and Shiloh, Y. (2006). Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat. Cell Biol. 8, 870–876.
Acknowledgments
This work was partially supported by the Intramural Research Program of the NIH, National Institute on Aging, and also by a Korean Research Foundation Grant of the Korean Government (MOEHRD) (KRF-2007-412-J00303, KRF-2007-521-C00211) to B. Ahn.
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Cheng, WH., Ahn, B., Bohr, V.A. (2009). Linking Human RecQ Helicases to DNA Damage Response and Aging. In: Khanna, K., Shiloh, Y. (eds) The DNA Damage Response: Implications on Cancer Formation and Treatment. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2561-6_15
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