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World Biochem 2019 & Regenerative Medicine 2019 Journal of Genetics and Molecular Biology | Volume 3
Page 25
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
YEARS
March 25-26, 2019 | Amsterdam, Netherlands
&
BIOCHEMISTRY AND ENZYMOLOGY
World Congress on
TISSUE ENGINEERING AND REGENERATIVE MEDICINE, STEM CELL RESEARCH
2nd Global Conference on
Joint Event on
MOLECULAR INSIGHTS INTO STRAND
DISPLACEMENT SYNTHESIS BY
DNA POLYMERASE: DISTAL RRRY
MOTIF AND TWO 3 HELIX BUNDLE
STRUCTURES ARE REQUIRED FOR SDSD
Strand displacement synthesis of DNA (SDSD) is an important process
that is required in the maturation of Okazaki fragments during the lag-
ging strand DNA synthesis. Using prototype E.coli DNA polymerase I (pol
I), we have shown that a structural motif consisting of three helix bundle in
the fingers subdomain (FS) is required for SDSD. We now show that, in ad-
dition to FS, a distal motif consisting of a conserved RRYR sequence span-
ning positions 821-824, and located at the junction of polymerase and 3’-5’
exonuclease domain of pol I, also participates in SDSD. The biochemical
results showed that alanine mutations of individual residues reduce DNA
binding affinity of enzyme by 5 – 35 – fold. We have previously reported
that the Y821 of RRYR motif regulates the proof-reading activity of pol I
suggesting at least two functions of RRYR motif. Furthermore, we have
identified another 3-helix bundle structure in the 5’-nuclease domain of
pol I. This motif is also necessary for efficient catalysis of SDSD. Hence, we
conclude that SDSD by pol I requires structural elements from its all three
domains. Interestingly, the 3 helix bundle resident tyrosine (Y215) is not
required for the 5’-nuclease activity. We further demonstrate that in DNA
polymerases, with active 3’ exonuclease, further cleavage of displaced
strand occurs in coordinated manner using intramolecular mode.
Mukund J Modak, J Genet Mol Biol 2019, Volume 3
Mukund J Modak is professor in Department
of Biochemistry and Molecular Biology. He
has completed his BSc in 1963 in University
of Poona in Maharashtra. He has complet-
ed his MSc in 1965 in University of Bombay,
Haffkine Institute, India and also completed
his PhD in 1965 from university of Bombay
Haffkine Institute.
Mukund J Modak
The State University of New Jersey, USA
BIOGRAPHY