Structure and mechanism of human PrimPol, a DNA polymerase with primase activity

Olga Rechkoblit, Yogesh K. Gupta, Radhika Malik, Kanagalaghatta R. Rajashankar, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

PrimPol is a novel human enzyme that contains both DNA primase and DNA polymerase activities. We present the first structure of human PrimPol in ternary complex with a DNA template-primer and an incoming deoxynucleoside triphosphate (dNTP). The ability of PrimPol to function as a DNA primase stems from a simple but remarkable feature-Almost complete lack of contacts to the DNA primer strand. This, in turn, allows two dNTPs to bind initiation and elongation sites on the enzyme for the formation of the first dinucleotide. PrimPol shows the ability to synthesize DNA opposite ultraviolet (UV) lesions; however, unexpectedly, the active-site cleft of the enzyme is constrained, which precludes the bypass of UV-induced DNA lesions by conventional translesion synthesis. Together, the structure addresses long-standing questions about how DNA primases actually initiate synthesis and how primase and polymerase activities combine in a single enzyme to carry out DNA synthesis.

Original languageEnglish (US)
Article numbere1601317
JournalScience advances
Volume2
Issue number10
DOIs
StatePublished - Oct 1 2016

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DNA Primase
DNA-Directed DNA Polymerase
DNA Primers
Enzymes
DNA
Catalytic Domain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rechkoblit, O., Gupta, Y. K., Malik, R., Rajashankar, K. R., Johnson, R. E., Prakash, L., ... Aggarwal, A. K. (2016). Structure and mechanism of human PrimPol, a DNA polymerase with primase activity. Science advances, 2(10), [e1601317]. https://doi.org/10.1126/sciadv.1601317

Structure and mechanism of human PrimPol, a DNA polymerase with primase activity. / Rechkoblit, Olga; Gupta, Yogesh K.; Malik, Radhika; Rajashankar, Kanagalaghatta R.; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.

In: Science advances, Vol. 2, No. 10, e1601317, 01.10.2016.

Research output: Contribution to journalArticle

Rechkoblit, O, Gupta, YK, Malik, R, Rajashankar, KR, Johnson, RE, Prakash, L, Prakash, S & Aggarwal, AK 2016, 'Structure and mechanism of human PrimPol, a DNA polymerase with primase activity', Science advances, vol. 2, no. 10, e1601317. https://doi.org/10.1126/sciadv.1601317
Rechkoblit O, Gupta YK, Malik R, Rajashankar KR, Johnson RE, Prakash L et al. Structure and mechanism of human PrimPol, a DNA polymerase with primase activity. Science advances. 2016 Oct 1;2(10). e1601317. https://doi.org/10.1126/sciadv.1601317
Rechkoblit, Olga ; Gupta, Yogesh K. ; Malik, Radhika ; Rajashankar, Kanagalaghatta R. ; Johnson, Robert E. ; Prakash, Louise ; Prakash, Satya ; Aggarwal, Aneel K. / Structure and mechanism of human PrimPol, a DNA polymerase with primase activity. In: Science advances. 2016 ; Vol. 2, No. 10.
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