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Originally published In Press as doi:10.1074/jbc.M305705200 on June 25, 2003

J. Biol. Chem., Vol. 278, Issue 36, 34685-34690, September 5, 2003
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The Frameshift Infidelity of Human DNA Polymerase {lambda}

IMPLICATIONS FOR FUNCTION*

Katarzyna Bebenek {ddagger} §, Miguel Garcia-Diaz § ¶, Luis Blanco ¶ and Thomas A. Kunkel {ddagger} ||

From the Laboratories of {ddagger}Molecular Genetics and Structural Biology, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709 and Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma, 28049 Madrid, Spain

DNA polymerase {lambda} (Pol {lambda}) is a member of the Pol X family having properties in common with several other mammalian DNA polymerases. To obtain clues to possible functions in vivo, we have determined the fidelity of DNA synthesis by human Pol {lambda}. The results indicate that the average single-base deletion error rate of Pol {lambda} is higher than those of other mammalian polymerases. In fact, unlike other DNA polymerases, Pol {lambda} generates single-base deletions at average rates that substantially exceed base substitution rates. Moreover, the sequence specificity for single-base deletions made by Pol {lambda} is different from that of other DNA polymerases and reveals that Pol {lambda} readily uses template-primers with limited base pair homology at the primer terminus. This ability, together with an ability to fill short gaps in DNA at low dNTP concentrations, is consistent with a role for mammalian Pol {lambda} in non-homologous end-joining. This may include non-homologous end-joining of strand breaks resulting from DNA damage, because Pol {lambda} has intrinsic 5',2'-deoxyribose-5-phosphate lyase activity.


Received for publication, June 2, 2003 , and in revised form, June 23, 2003.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ These authors contributed equally to this work.

|| To whom correspondence should be addressed. Tel.: 919-541-2644; Fax: 919-541-7613; E-mail: kunkel{at}niehs.nih.gov.


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