Crystal structure of the catalytic core of human DNA polymerase kappa

Sacha N. Uljon, Robert E. Johnson, Thomas A. Edwards, Satya Prakash, Louise Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

We present the crystal structure of the catalytic core of human DNA polymerase kappa (hPolκ), the first structure of a human Y-family polymerase. hPolκ is implicated in the proficient extension of mispaired primer termini on undamaged DNAs, and in the extension step of lesion bypass. The structure reveals a stubby "fingers" subdomain, which despite its small size appears to be tightly restrained with respect to a putative templating base. The structure also reveals a novel "thumb" subdomain that provides a basis for the importance of the N-terminal extension unique to hPolκ. And, most surprisingly, the structure reveals the polymerase-associated domain (PAD) juxtaposed on the dorsal side of the "palm" subdomain, as opposed to the fingers subdomain. Together, these properties suggest that the hPolκ active site is constrained at the site of the templating base and incoming nucleotide, but the polymerase is less constrained following translocation of the lesion.

Original languageEnglish (US)
Pages (from-to)1395-1404
Number of pages10
JournalStructure
Volume12
Issue number8
DOIs
StatePublished - Aug 2004

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Fingers
Catalytic Domain
Thumb
Nucleotides
DNA
human POLK protein

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Crystal structure of the catalytic core of human DNA polymerase kappa. / Uljon, Sacha N.; Johnson, Robert E.; Edwards, Thomas A.; Prakash, Satya; Prakash, Louise; Aggarwal, Aneel K.

In: Structure, Vol. 12, No. 8, 08.2004, p. 1395-1404.

Research output: Contribution to journalArticle

Uljon, Sacha N. ; Johnson, Robert E. ; Edwards, Thomas A. ; Prakash, Satya ; Prakash, Louise ; Aggarwal, Aneel K. / Crystal structure of the catalytic core of human DNA polymerase kappa. In: Structure. 2004 ; Vol. 12, No. 8. pp. 1395-1404.
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