Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility

Irina Voineagu; Christine F. Surka; Alexander A. Shishkin; Maria M. Krasilnikova; Sergei M. Mirkin

doi:10.1038/nsmb.1527

Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility

Irina Voineagu
, Christine F. Surka
, Alexander A. Shishkin
, Maria M. Krasilnikova
, Sergei M. Mirkin

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

109 Scopus citations

Abstract

Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Saccharomyces cerevisiae proteins Tof1 and Mrc1 facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint.

Original language	English (US)
Pages (from-to)	226-228
Number of pages	3
Journal	Nature Structural and Molecular Biology
Volume	16
Issue number	2
DOIs	https://doi.org/10.1038/nsmb.1527
State	Published - Feb 2009

All Science Journal Classification (ASJC) codes

Structural Biology
Molecular Biology

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10.1038/nsmb.1527

Cite this

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title = "Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility",

abstract = "Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Saccharomyces cerevisiae proteins Tof1 and Mrc1 facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint.",

author = "Irina Voineagu and Surka, \{Christine F.\} and Shishkin, \{Alexander A.\} and Krasilnikova, \{Maria M.\} and Mirkin, \{Sergei M.\}",

note = "Funding Information: We thank K. Mirkin for her help with plasmid construction, C. Freudenreich for many useful suggestions, S. Elledge (Harvard Medical School) for the plasmid with the mrc1AQ allele and J. and P. White for their generosity. Supported by the US National Institutes of Health grant GM60987 to S.M.M.",

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AU - Voineagu, Irina

AU - Surka, Christine F.

AU - Shishkin, Alexander A.

AU - Krasilnikova, Maria M.

AU - Mirkin, Sergei M.

N1 - Funding Information: We thank K. Mirkin for her help with plasmid construction, C. Freudenreich for many useful suggestions, S. Elledge (Harvard Medical School) for the plasmid with the mrc1AQ allele and J. and P. White for their generosity. Supported by the US National Institutes of Health grant GM60987 to S.M.M.

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N2 - Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Saccharomyces cerevisiae proteins Tof1 and Mrc1 facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint.

AB - Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Saccharomyces cerevisiae proteins Tof1 and Mrc1 facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint.

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JO - Nature Structural and Molecular Biology

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IS - 2

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Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility

Abstract

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