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The block of DNA polymerase delta strand displacement activity by an abasic site can be rescued by the concerted action of DNA polymerase beta and Flap endonuclease 1.


Maga, G; van Loon, B; Crespan, E; Villani, G; Hübscher, U (2009). The block of DNA polymerase delta strand displacement activity by an abasic site can be rescued by the concerted action of DNA polymerase beta and Flap endonuclease 1. Journal of Biological Chemistry, 284(21):14267-1475.

Abstract

Abasic (AP) sites are very frequent and dangerous DNA lesions. Their ability to block the advancement of a replication fork has been always viewed as a consequence of their inhibitory effect on the DNA synthetic activity of replicative DNA polymerases (DNA pols). Here we show that AP sites can also affect the strand displacement activity of the lagging strand DNA pol delta, thus preventing proper Okazaki fragment maturation. This block can be overcome through a polymerase switch, involving the combined physical and functional interaction of DNA pol beta and Flap endonuclease 1. Our data identify a previously unnoticed deleterious effect of the AP site lesion on normal cell metabolism and suggest the existence of a novel repair pathway that might be important in preventing replication fork stalling.

Abstract

Abasic (AP) sites are very frequent and dangerous DNA lesions. Their ability to block the advancement of a replication fork has been always viewed as a consequence of their inhibitory effect on the DNA synthetic activity of replicative DNA polymerases (DNA pols). Here we show that AP sites can also affect the strand displacement activity of the lagging strand DNA pol delta, thus preventing proper Okazaki fragment maturation. This block can be overcome through a polymerase switch, involving the combined physical and functional interaction of DNA pol beta and Flap endonuclease 1. Our data identify a previously unnoticed deleterious effect of the AP site lesion on normal cell metabolism and suggest the existence of a novel repair pathway that might be important in preventing replication fork stalling.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease
Dewey Decimal Classification:570 Life sciences; biology
Date:2009
Deposited On:01 Mar 2010 14:51
Last Modified:21 Nov 2017 14:47
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in: Maga, G; van Loon, B; Crespan, E; Villani, G; Hübscher, U (2009). The block of DNA polymerase delta strand displacement activity by an abasic site can be rescued by the concerted action of DNA polymerase beta and Flap endonuclease 1. Journal of Biological Chemistry, 284(21):14267-1475. © the American Society for Biochemistry and Molecular Biology.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1074/jbc.M900759200
PubMed ID:19329428

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