Skip to main content
SpringerLink
Log in

Age-Related Decline in DNA Polymerase β Activity in Rat Brain and Tissues

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Fidelity of DNA polymerases is vital for maintaining genomic integrity. Deficient DNA repair leads to age related disorders or cancer. If the age at which the decline in activity of predominant DNA repair enzymes starts is identified, and the deficient proteins supplemented, then the manifestation of these diseases can be delayed promoting healthy aging. DNA polymerase β (pol β) is a predominant repair enzyme in brain. DNA pol β activity declines with age in rat brain/neurons but the exact age during the life time of rat when this decline begins is not known, and comparison of this activity was not made between post mitotic and proliferating tissues therefore the pattern of pol β with age was studied in rat brain and tissues. The decline in pol β activity started between 30 and 45 days postnatal in all the tissues. Post mitotic tissues showed pronounced decline than the proliferating tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

pols:

DNA polymerases

pol β:

DNA polymerase β

BER:

Base excision repair

NHEJ:

Non-homologous end joining

PPO:

2,5-di(phenyl)–1,3–oxazole

POPOP:

2,2′-p-phenylene-bis [5-phenyloxazole]

References

  1. Loeb LA, Monnat RJ Jr (2008) DNA polymerases and human disease. Nat Rev Genet 9:594–604

    Article  PubMed  CAS  Google Scholar 

  2. Hubscher U, Kuenzle CC, Spadari S (1977) Variation of DNA polymerases-alpha, -beta. and -gamma during perinatal tissue growth and differentiation. Nucleic Acids Res 4:2917–2929

    Article  PubMed  CAS  Google Scholar 

  3. Hanaoka F, Sayato J, Arai H, Hasegawa N, Inui N, Mitsui Y, Yamada M (1983) Changes in DNA polymerases alpha, beta and gamma in mouse liver as a function of age. Mech Ageing Dev 23:315–327

    Article  PubMed  CAS  Google Scholar 

  4. Kaneko T, Tahara S, Tanno M, Taguchi T (2002) Age-related changes in the induction of DNA polymerases in rat liver by gamma-ray irradiation. Mech Ageing Dev 123:1521–1528

    Article  PubMed  CAS  Google Scholar 

  5. Waser J, Hubscher U, Spadari S, Kuenzle CC (1979) DNA polymerase-beta from brain neurons is a repair enzyme. Eur J Biochem 97:361–368

    Article  PubMed  CAS  Google Scholar 

  6. Subba Rao KV, Subba Rao K (1984) Increased DNA polymerase beta-activity in different regions of aging rat brain. Biochem Int 9:391–397

    PubMed  CAS  Google Scholar 

  7. Starcevic D, Dalal S, Sweasy JB (2004) Is there a link between DNA polymerase beta and cancer? Cell Cycle 3:998–1001

    Article  PubMed  CAS  Google Scholar 

  8. Cabelof DC, Ikeno Y, Nyska A, Busuttil RA, Anyangwe N, Vijg J, Matherly LH, Tucker JD, Wilson SH, Richardson A, Heydari AR (2006) Haploinsufficiency in DNA polymerase beta increases cancer risk with age and alters mortality rate. Cancer Res 66:7460–7465

    Article  PubMed  CAS  Google Scholar 

  9. Prapurna DR, Rao KS (1997) DNA polymerases delta and epsilon in developing and aging rat brain. Int J Dev Neurosci 15:67–73

    Article  PubMed  CAS  Google Scholar 

  10. Rao KS (1993) Genomic damage and its repair in young and aging brain. Mol Neurobiol 7:23–48

    Article  PubMed  CAS  Google Scholar 

  11. Rao KS (1997) DNA-damage & DNA-repair in ageing brain. Indian J Med Res 106:423–437

    PubMed  CAS  Google Scholar 

  12. Subrahmanyam K, Rao KS (1988) On the type of DNA polymerase activity in neuronal, astroglial, and oligodendroglial cell fractions from young, adult, and old rat brains. Biochem Int 16:1111–1117

    PubMed  CAS  Google Scholar 

  13. Raji NS, Krishna TH, Rao KS (2002) DNA-polymerase alpha, beta, delta and epsilon activities in isolated neuronal and astroglial cell fractions from developing and aging rat cerebral cortex. Int J Dev Neurosci 20:491–496

    Article  PubMed  CAS  Google Scholar 

  14. Subba Rao K, Martin GM, Loeb LA (1985) Fidelity of DNA polymerase-beta in neurons from young and very aged mice. J Neurochem 45:1273–1278

    Article  PubMed  CAS  Google Scholar 

  15. Rao KS, Vinay Kumar D, Bhaskar MS, Sripad G (1994) On the ‘active’ molecules of DNA-polymerase beta in aging rat brain. Biochem Mol Biol Int 34:287–294

    PubMed  CAS  Google Scholar 

  16. Krishna TH, Mahipal S, Sudhakar A, Sugimoto H, Kalluri R, Rao KS (2005) Reduced DNA gap repair in aging rat neuronal extracts and its restoration by DNA polymerase beta and DNA-ligase. J Neurochem 92:818–823

    Article  PubMed  CAS  Google Scholar 

  17. Rao KS, Annapurna VV, Raji NS (2001) DNA polymerase-beta may be the main player for defective DNA repair in aging rat neurons. Ann N Y Acad Sci 928:113–120

    Article  PubMed  CAS  Google Scholar 

  18. Rao KS, Annapurna VV, Raji NS, Harikrishna T (2000) Loss of base excision repair in aging rat neurons and its restoration by DNA polymerase beta. Brain Res Mol Brain Res 85:251–259

    Article  PubMed  CAS  Google Scholar 

  19. Rao KS (2007) DNA repair in aging rat neurons. Neuroscience 145:1330–1340

    Article  PubMed  CAS  Google Scholar 

  20. Subba Rao K (2007) Mechanisms of disease: DNA repair defects and neurological disease. Nat Clin Pract Neurol 3:162–172

    Article  PubMed  Google Scholar 

  21. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  22. Serra I, Vanella A, Avola R, Giuffrida AM (1982) DNA polymerase and thymidine kinase activities in different regions of rat brain during postnatal development: effect of undernutrition. Neurochem Res 7:943–951

    Article  PubMed  CAS  Google Scholar 

  23. Xu G, Herzig M, Rotrekl V, Walter CA (2008) Base excision repair, aging and health span. Mech Ageing Dev 129:366–382

    Article  PubMed  CAS  Google Scholar 

  24. Cabelof DC, Raffoul JJ, Ge Y, Van Remmen H, Matherly LH, Heydari AR (2006) Age-related loss of the DNA repair response following exposure to oxidative stress. J Gerontol A Biol Sci Med Sci 61:427–434

    Article  PubMed  Google Scholar 

  25. Intano GW, Cho EJ, McMahan CA, Walter CA (2003) Age-related base excision repair activity in mouse brain and liver nuclear extracts. J Gerontol A Biol Sci Med Sci 58:205–211

    Article  PubMed  Google Scholar 

  26. Cabelof DC, Raffoul JJ, Yanamadala S, Guo Z, Heydari AR (2002) Induction of DNA polymerase beta-dependent base excision repair in response to oxidative stress in vivo. Carcinogenesis 23:1419–1425

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Indian Council of Medical Research (ICMR) New Delhi. Council of Scientific and Industrial Research (CSIR) is thanked for the Senior Research Fellowship and contingency grant to V. N. Vyjayanti and U.Swain. We thank Mr. Govardhan chary for maintaining the animals.

Author information

Author notes

  1. Kalluri Subba Rao

    Present address: Center for Biotechnology, Institute of Science and Technology, Jawaharlal Nehru Technological University, Hyderabad, Andhra Pradesh, 500 085, India

Authors and Affiliations

  1. Department of Biochemistry, University of Hyderabad, Hyderabad, Andhra Pradesh, 500046, India

    V. N. Vyjayanti, Umakanta Swain & Kalluri Subba Rao

Authors
  1. V. N. Vyjayanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Umakanta Swain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kalluri Subba Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kalluri Subba Rao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vyjayanti, V.N., Swain, U. & Rao, K.S. Age-Related Decline in DNA Polymerase β Activity in Rat Brain and Tissues. Neurochem Res 37, 991–995 (2012). https://doi.org/10.1007/s11064-011-0694-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-011-0694-9

Keywords

Search

Navigation