ANALISIS BIOINFORMATIKA MUTASI S228I PROTEIN PCNA DAN PENGARUHNYA PADA STRUKTUR 3 DIMENSI PROTEIN

Syarifah Dewi

Abstract


Proliferating cell nuclear antigen (PCNA) adalah protein penjepit DNA yang meningkatkan efektivitas kerja DNA polimerase eukariot. Protein ini mempunyai struktur berbentuk cincin yang mengelilingi DNA dan meningkatkan processivity pada proses replikasi DNA. Mutasi titik pada gen PCNA manusia, Ser228Ile, akan menghasilkan kelainan autosomal resesif dengan gejala penyakit gangguan perbaikan kerusakan DNA seperti Xeroderma pigmentosum, Cockayne syndrome, dan Ataxia telangiectasia. Mutasi ini letaknya berdekatan dengan dengan situs pengikatan protein pengikat PCNA. Mutasi Ser228Ile pada protein PCNA akan menyebabkan perubahan pada struktur IDCL (interdomain connecting loop) dan PIPbinding pocket sehingga mengganggu pengikatan protein ligan ke PCNA dan fungsinya yang sebagian besar berhubungan dengan proses replikasi dan perbaikan DNA

Full Text:

PDF

References


Bacquin, A. et al. 2013. The helicase FBH1 is tightly regulated by PCNA via CRL4(Cdt2)mediated proteolysis in human cells. Nucleic Acids Res. 41, 6501–6513

Baple, E. L., Chambers, H., Cross, H. E., Fawcett, H., Nakazawa, Y., Chioza, B. A., Harlalka, G. V., Mansour, S., Sreekantan-Nair, A., Patton, M. A., Muggenthaler, M., Rich, P., and 10 others. Hypomorphic PCNA mutation underlies a human DNA repair disorder. J. Clin. Invest. 124: 3137-3146, 2014.

Ciccia, A. et al. 2012. Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. Mol. Cell 47, 396–409

Duffy CM, Hilbert BJ, KelchBA. A DiseaseCausing Variant in PCNA Disrupts a Promiscuous Protein Binding Site. J Mol Biol (2016) 428, 1023–1040.

Egelkrout EM, Mariconti L, Settlage SB, Cella R, Robertson D, Hanley-Bowdoin L (2002). “Two E2F elements regulate the proliferating cell nuclear antigen promoter differently during leaf developmentâ€. Plant Cell 14 (12): 3225–3236.

Fander, B., Moldovan, G.L., Sacher, M., Hoege, C., and Jentsch, S. 2005. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature 436, 428–433.

Gilljam, K.M. et al. 2009. Identification of a novel, widespread, and functionally important PCNA-binding motif. J. Cell Biol. 186, 645– 654

Hoege, C. et al. 2002. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419, 135–141

J.M. Gulbis, Z. Kelman, J. Hurwitz, M. O'Donnell, J. Kuriyan, Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA, Cell 87 (1996) 297–306.

Lambert, S., Watson, A., Sheedy, D.M., Martin, B., and Carr, A.M. 2005. Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier. Cell 121, 689–702.

Lehmann AR, Fuchs RP (December 2006). Gaps and forks in DNA replication: Rediscovering old models. DNA Repair (Amst.) 5 (12): 1495–1498

Moldovan GL, Pfander B, Jentsch S. 2007. PCNA, the maestro of the replication fork. Cell 129 (4): 665–79.

Muller, R. et al. 2013. Targeting proliferating cell nuclear antigen and its protein interactions induces apoptosis in multiple myeloma cells. PLoS ONE 8, e70430

P. McInerney, A. Johnson, F. Katz, M. O'Donnell. 2007. Characterization of a triple DNA polymerase replisome. Mol. Cell 27. 527– 538

R. Maiti, G.H. Van Domselaar, H. Zhang, D.S. Wishart. 2004. SuperPose: A simple server

for sophisticated structural superposition, Nucleic Acids Res. 32. W590–W594

R. McNally, G.D. Bowman, E.R. Goedken, M. O'Donnell, J. Kuriyan. 2010. Analysis of the role of PCNA–DNA contacts during clamp loading, BMC Struct. Biol. 10, 3

T.R. Beattie, S.D. Bel. 2012. Coordination of multiple enzyme activities by a single PCNA in archaeal Okazaki fragment maturation, EMBO J. 3; 1556–1567

Ulrich, H.D. and Walden, H. 2010. Ubiquitin signalling in DNA replication and repair. Nat. Rev. Mol. Cell Biol. 11, 479–489

Wang, S-C. et al. 2006. Tyrosine phosphorylation controls PCNA function through protein stability. Nat. Cell Biol. 8, 1359–1368

Warbrick, E. 2000. The puzzle of PCNA’s many partners. Bioessays 22, 997–1006

Zhang G, Gibbs E, Kelman Z, O'Donnell M, Hurwitz J. 1999. Studies on the interactions between human replication factor C and human proliferating cell nuclear antigen. Proc. Natl. Acad. Sci. U.S.A. 96 (5): 1869– 1874.


Refbacks

  • There are currently no refbacks.





Indonesian Journal of Biotechnology and Biodiversity

ISSN 2581-0014

published by:

Department of Biotechnology, Faculty of Health, Universitas Esa Unggul

Jalan Arjuna Utara No. 9, Kebon Jeruk, Jakarta Barat