THE REPLISOME

Genome duplication requires tight coordination between parental duplex-DNA unwinding and daughter-strand synthesis within the replisome, to prevent the accumulation of vulnerable single-stranded DNA segments and the onset of genomic instability.

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We are interested in understanding replisome biogenesis and the mechanism of coupled DNA unwinding and synthesis at the replication fork.

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Relevant papers

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Goswami P, Abid Ali F, Douglas M, Locke J, Purkiss A, Janska A, Eickhoff P, Early A, Nans A, Cheung A, Diffley JF, Costa A. CRYO-EM STRUCTURE OF DNA-CMG-POL EPSILON ELUCIDATES THE ROLES OF ESSENTIAL, NON-CATALYTIC POLYMERASE MODULES IN THE EUKARYOTIC REPLISOME. Nature Commun. In press.

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Swuec P, Renault L, Borg A, Shah F, Murphy VJ, van Twest S, Snijders AP, Deans AJ, Costa A. THE FA CORE COMPLEX CONTAINS A HOMO-DIMERIC CATALYTIC MODULE FOR THE SYMMETRIC MONO-UBIQUITINATION OF FANCI-FANCD2. Cell Rep. 2017 Jan 17;18(3):611-623.

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Zhou JC, Janska A, Goswami P, Renault L, Abid Ali F, Kotecha A, Diffley JF, Costa A. CMG-POL EPSILON DYNAMICS SUGGESTS A MECHANISM FOR THE ESTABLISHMENT OF LEADING-STRAND SYNTHESIS IN THE EUKARYOTIC REPLISOME. PNAS. 2017 Apr 3.

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Samora CP, Saksouk J, Goswami P, Wade BO, Singleton MR, Bates PA, Lengronne A, Costa A, Uhlmann F. CTF4 LINKS DNA REPLICATION WITH SISTER CHROMATID COHESION ESTABLISHMENT BY RECRUITING THE CHL1 HELICASE TO THE REPLISOME. Mol Cell. 2016 Aug 4;63(3):371-84. (Preview in Mol Cell Aug 4;63(3): 347–348).

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Pellegrini L*, Costa A*. NEW INSIGHTS INTO THE MECHANISM OF DNA DUPLICATION BY THE EUKARYOTIC REPLISOME. Trends in Biochem Sci 2016 Oct;41(10):859-71 (*corresponding authors).

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Simon AC, Zhou JC, Perera RL, van Deursen F, Evrin C, Ivanova ME, Kilkenny ML, Renault L, Kjaer S, Matak-Vinković D, Labib K, Costa A*, Pellegrini L*. A CTF4 TRIMER COUPLES THE CMG HELICASE TO DNA PO­­­LYMERASE a IN THE EUKARYOTIC REPLISOME. Nature. 2014 Jun 12;510(7504):293-7. (*corresponding authors, rated ‘exceptional’ on f1000.com).