Differential regulation of expression of the mammalian dna repair genes by growth stimulation

ABSTRACT During DNA replication, DNA becomes more vulnerable to certain DNA damages. DNA repair genes involved in repair of the damages may be induced by growth stimulation. However,

regulation of DNA repair genes by growth stimulation has not been analysed in detail. In this report, we analysed the regulation of expression of mammalian _MSH2_, _MSH3_ and _MLH1_ genes

involved in mismatch repair, and _Rad51_ and _Rad50_ genes involved in homologous recombination repair, in relation to cell growth. Unexpectedly, we found a clear difference in regulation of

these repair gene expression by growth stimulation even in the same repair system. The expression of _MSH2_, _MLH1_ and _Rad51_ genes was clearly growth regulated, whereas _MSH3_ and

_Rad50_ genes were constitutively expressed, suggesting differential requirement of the repair gene products for cell proliferation. _MSH3_ gene is located in a bidirectionally divergent

manner with _DHFR_ gene that is regulated by growth stimulation, indicating that bidirectionally divergent promoters are not necessarily coordinately regulated. Promoter analysis showed that

the growth-regulated expression of _MLH1_ and _Rad51_ genes was mainly mediated by E2F that plays crucial roles in regulation of DNA replication, suggesting close relation between some of

the repair genes and DNA replication. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through

your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant

access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions *

Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS RAD27 AND EXO1 FUNCTION IN DIFFERENT EXCISION PATHWAYS FOR MISMATCH REPAIR IN _SACCHAROMYCES CEREVISIAE_

Article Open access 22 September 2021 E2F-DEPENDENT TRANSCRIPTION DETERMINES REPLICATION CAPACITY AND S PHASE LENGTH Article Open access 14 July 2020 MITOTIC DNA SYNTHESIS IN RESPONSE TO

REPLICATION STRESS REQUIRES THE SEQUENTIAL ACTION OF DNA POLYMERASES ZETA AND DELTA IN HUMAN CELLS Article Open access 09 February 2023 REFERENCES * Adachi N and Lieber MR . (2002). _Cell_,

109, 807–809. * Benson FE, Baumann P and West SC . (1998). _Nature_, 391, 401–404. * Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL and Baskaran R . (2003). _Nat. Genet._, 33,

80–84. * Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates III JR, Hays L, Morgan WF and Petrini JH . (1998). _Cell_, 93, 477–486. * Claij N and Te Riele H . (2002). _Oncogene_,

21, 2873–2879. * Clever B, Interthal H, Schmuckli-Maurer J, King J, Sigrist M and Heyer WD . (1997). _EMBO J._, 16, 2535–2544. * Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan

DA and Petrini JH . (1996). _Mol. Cell. Biol._, 16, 4832–4841. * Drummond JT, Genschel J, Wolf E and Modrich P . (1997). _Proc. Natl. Acad. Sci. USA_, 94, 10144–10149. * Dyson N . (1998).

_Genes Dev._, 12, 2245–2262. * Hawn MT, Umar A, Carethers JM, Marra G, Kunkel TA, Boland CR and Koi M . (1995). _Cancer Res._, 55, 3721–3725. * Ikeda MA, Jakoi L and Nevins JR . (1996).

_Proc. Natl. Acad. Sci. USA_, 93, 3215–3220. * Ishida S, Huang E, Zuzan H, Spang R, Leone G, West M and Nevins JR . (2001). _Mol. Cell. Biol._, 21, 4684–4699. * Ito E, Yanagisawa Y, Iwahashi

Y, Suzuki Y, Nagasaki H, Akiyama Y, Sugano S, Yuasa Y and Maruyama K . (1999). _Biochem. Biophys. Res. Commun._, 256, 488–494. * Iwahashi Y, Ito E, Yanagisawa Y, Akiyama Y, Yuasa Y, Onodera

T and Maruyama K . (1998). _Gene_, 213, 141–147. * Iwanaga R, Ohtani K, Hayashi T and Nakamura M . (2001). _Oncogene_, 20, 2055–2067. * Johnson DG, Ohtani K and Nevins JR . (1994). _Genes

Dev._, 8, 1514–1525. * Lin WC, Lin FT and Nevins JR . (2001). _Genes Dev._, 15, 1833–1844. * Marra G, Iaccarino I, Lettieri T, Roscilli G, Delmastro P and Jiricny J . (1998). _Proc. Natl.

Acad. Sci. USA_, 95, 8568–8573. * Meyers M, Theodosiou M, Acharya S, Odegaard E, Wilson T, Lewis JE, Davis TW, Wilson-Van Patten C, Fishel R and Boothman DA . (1997). _Cancer Res._, 57,

206–208. * Mizuta R, LaSalle JM, Cheng HL, Shinohara A, Ogawa H, Copeland N, Jenkins NA, Lalande M and Alt FW . (1997). _Proc. Natl. Acad. Sci. USA_, 94, 6927–6932. * Nevins JR, Leone G,

DeGregori J and Jakoi L . (1997). _J. Cell. Physiol._, 173, 233–236. * Ohtani K . (1999). _Front. Biosci._, 4, D793–804. * Ohtani K, Iwanaga R, Nakamura M, Ikeda M, Yabuta N, Tsuruga H and

Nojima H . (1999). _Oncogene_, 18, 2299–2309. * Ohtani K, Tsujimoto A, Ikeda M and Nakamura M . (1998). _Oncogene_, 17, 1777–1785. * Peltomaki P . (2001). _Mutat. Res._, 488, 77–85. *

Polager S, Kalma Y, Berkovich E and Ginsberg D . (2002). _Oncogene_, 21, 437–446. * Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA and Dynlacht BD . (2002). _Genes Dev._, 16,

245–256. * Schwarz JK, Bassing CH, Kovesdi I, Datto MB, Blazing M, George S, Wang XF and Nevins JR . (1995). _Proc. Natl. Acad. Sci. USA_, 92, 483–487. * Shimada T, Fujii H and Lin H .

(1989). _J. Biol. Chem._, 264, 20171–20174. * Slansky JE, Li Y, Kaelin WG and Farnham PJ . (1993). _Mol. Cell. Biol._, 13, 1610–1618. * Weinmann AS, Yan PS, Oberley MJ, Huang TH and Farnham

PJ . (2002). _Genes Dev._, 16, 235–244. * West SC . (2003). _Nat. Rev. Mol. Cell. Biol._, 4, 435–445. * Wilson TM, Ewel A, Duguid JR, Eble JN, Lescoe MK, Fishel R and Kelley MR . (1995).

_Cancer Res._, 55, 5146–5150. * Yamamoto A, Taki T, Yagi H, Habu T, Yoshida K, Yoshimura Y, Yamamoto K, Matsushiro A, Nishimune Y and Morita T . (1996). _Mol. Gen. Genet._, 251, 1–12. *

Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD and Lee WH . (1999). _Science_, 285, 747–750. * Zhu XD, Kuster B, Mann M, Petrini JH and de Lange T . (2000). _Nat.

Genet._, 25, 347–352. Download references ACKNOWLEDGEMENTS We thank K Maruyama, Y Yuasa, E Ito, Y Iwahashi and Y Yanagisawa for the reporter plasmids. We also thank S Morinaga for excellent

technical assistance. This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from The Ministry of Education, Culture, Sports, Science and Technology. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan Ritsuko Iwanaga, Hideyuki Komori 

& Kiyoshi Ohtani Authors * Ritsuko Iwanaga View author publications You can also search for this author inPubMed Google Scholar * Hideyuki Komori View author publications You can also

search for this author inPubMed Google Scholar * Kiyoshi Ohtani View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to

Kiyoshi Ohtani. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Iwanaga, R., Komori, H. & Ohtani, K. Differential regulation of expression of the

mammalian DNA repair genes by growth stimulation. _Oncogene_ 23, 8581–8590 (2004). https://doi.org/10.1038/sj.onc.1207976 Download citation * Received: 02 April 2004 * Revised: 09 June 2004

* Accepted: 16 June 2004 * Published: 27 September 2004 * Issue Date: 11 November 2004 * DOI: https://doi.org/10.1038/sj.onc.1207976 SHARE THIS ARTICLE Anyone you share the following link

with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt

content-sharing initiative KEYWORDS * DNA repair gene * cell growth * gene expression * E2F