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

Kannouche, P., Fernandez De Henestrosa, A. R., Coull, B., Vidal, A. E., Gray, C., Zicha, D., Woodgate, R. and Lehmann, A. R. (2002) Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells. EMBO Journal, 21 (22). pp. 6246-6256. 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: Article
Additional Information: GDSC34
Depositing User: Gee Wheatley
Date Deposited: 02 Apr 2007
Last Modified: 14 Jun 2012 10:48
URI: http://sro.sussex.ac.uk/id/eprint/1050
Google Scholar:141 Citations
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