Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells

Kannouche, Patricia and Fernández de Henestrosa, Antonio R and Coull, Barry and Vidal, Antonio E and Gray, Colin and Zicha, Daniel and Woodgate, Roger and Lehmann, Alan R (2003) Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells. EMBO Journal, 21 (22). pp. 1223-33. ISSN 0261-4189

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Abstract

Y-family DNA polymerases can replicate past a variety of damaged bases in vitro but, with the exception of DNA polymerase eta (poleta), which is defective in xeroderma pigmentosum variants, there is little information on the functions of these polymerases in vivo. Here, we show that DNA polymerase iota (poliota), like poleta, associates with the replication machinery and accumulates at stalled replication forks following DNA-damaging treatment. We show that poleta and poliota foci form with identical kinetics and spatial distributions, suggesting that localization of these two polymerases is tightly co-ordinated within the nucleus. Furthermore, localization of poliota in replication foci is largely dependent on the presence of poleta. Using several different approaches, we demonstrate that poleta and poliota interact with each other physically and that the C-terminal 224 amino acids of poliota are sufficient for both the interaction with poleta and accumulation in replication foci. Our results provide strong evidence that poleta targets poliota to the replication machinery, where it may play a general role in maintaining genome integrity as well as participating in translesion DNA synthesis.

Item Type:
Journal Article
Journal or Publication Title:
EMBO Journal
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2400
Subjects:
ID Code:
136255
Deposited By:
Deposited On:
21 Aug 2019 13:10
Refereed?:
Yes
Published?:
Published
Last Modified:
11 Mar 2020 07:40