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Cancer-associated variant expression and interaction of CIZ1 with cyclin A1 in differentiating male germ cells

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Cancer-associated variant expression and interaction of CIZ1 with cyclin A1 in differentiating male germ cells. / Greaves, Erin A.; Copeland, Nikki A.; Coverley, Dawn; Ainscough, Justin F. X.

In: Journal of Cell Science, Vol. 125, 15.05.2012, p. 2466-2477.

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Greaves, Erin A. ; Copeland, Nikki A. ; Coverley, Dawn ; Ainscough, Justin F. X. / Cancer-associated variant expression and interaction of CIZ1 with cyclin A1 in differentiating male germ cells. In: Journal of Cell Science. 2012 ; Vol. 125. pp. 2466-2477.

Bibtex

@article{038fa7b79e3c4366b0ca17788f2ec1ff,
title = "Cancer-associated variant expression and interaction of CIZ1 with cyclin A1 in differentiating male germ cells",
abstract = "CIZ1 is a nuclear matrix associated DNA replication factor unique to higher eukaryotes, for which alternatively spliced isoforms have been associated with a range of disorders. In vitro the CIZ1 N-terminus interacts with cyclins E and A via distinct sites, enabling functional cooperation with cyclin A-Cdk2 to promote replication initiation. C-terminal sequences anchor CIZ1 to fixed sites on the nuclear matrix imposing spatial constraint on cyclin dependent kinase activity. Here we demonstrate that CIZ1 is predominantly expressed as predicted full-length product throughout mouse development, consistent with a ubiquitous role in cell and tissue renewal. CIZ1 is expressed in proliferating stem cells of the testis, but is notably down-regulated following commitment to differentiation. Significantly, CIZ1 is re-expressed at high levels in non-proliferative spermatocytes prior to meiotic division. Sequence analysis identifies at least seven alternatively spliced variants at this time, including a dominant cancer-associated form and a set of novel isoforms. Furthermore, we show that in these post-replicative cells CIZ1 interacts with the germ cell specific cyclin, A1, that has been implicated in DNA double-strand break repair. Consistent with this role, antibody depletion of CIZ1 reduces the capacity for testis extract to repair digested plasmid DNA in vitro. Together, the data imply novel post-replicative roles for CIZ1 in germ cell differentiation that may include meiotic recombination, a process intrinsic to genome stability and diversification.",
keywords = "Alternative splicing , Cancer , CIZ1 , Cyclin A1 , Development , Male germ cell",
author = "Greaves, {Erin A.} and Copeland, {Nikki A.} and Dawn Coverley and Ainscough, {Justin F. X.}",
year = "2012",
month = may,
day = "15",
doi = "10.1242/jcs.101097",
language = "English",
volume = "125",
pages = "2466--2477",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",

}

RIS

TY - JOUR

T1 - Cancer-associated variant expression and interaction of CIZ1 with cyclin A1 in differentiating male germ cells

AU - Greaves, Erin A.

AU - Copeland, Nikki A.

AU - Coverley, Dawn

AU - Ainscough, Justin F. X.

PY - 2012/5/15

Y1 - 2012/5/15

N2 - CIZ1 is a nuclear matrix associated DNA replication factor unique to higher eukaryotes, for which alternatively spliced isoforms have been associated with a range of disorders. In vitro the CIZ1 N-terminus interacts with cyclins E and A via distinct sites, enabling functional cooperation with cyclin A-Cdk2 to promote replication initiation. C-terminal sequences anchor CIZ1 to fixed sites on the nuclear matrix imposing spatial constraint on cyclin dependent kinase activity. Here we demonstrate that CIZ1 is predominantly expressed as predicted full-length product throughout mouse development, consistent with a ubiquitous role in cell and tissue renewal. CIZ1 is expressed in proliferating stem cells of the testis, but is notably down-regulated following commitment to differentiation. Significantly, CIZ1 is re-expressed at high levels in non-proliferative spermatocytes prior to meiotic division. Sequence analysis identifies at least seven alternatively spliced variants at this time, including a dominant cancer-associated form and a set of novel isoforms. Furthermore, we show that in these post-replicative cells CIZ1 interacts with the germ cell specific cyclin, A1, that has been implicated in DNA double-strand break repair. Consistent with this role, antibody depletion of CIZ1 reduces the capacity for testis extract to repair digested plasmid DNA in vitro. Together, the data imply novel post-replicative roles for CIZ1 in germ cell differentiation that may include meiotic recombination, a process intrinsic to genome stability and diversification.

AB - CIZ1 is a nuclear matrix associated DNA replication factor unique to higher eukaryotes, for which alternatively spliced isoforms have been associated with a range of disorders. In vitro the CIZ1 N-terminus interacts with cyclins E and A via distinct sites, enabling functional cooperation with cyclin A-Cdk2 to promote replication initiation. C-terminal sequences anchor CIZ1 to fixed sites on the nuclear matrix imposing spatial constraint on cyclin dependent kinase activity. Here we demonstrate that CIZ1 is predominantly expressed as predicted full-length product throughout mouse development, consistent with a ubiquitous role in cell and tissue renewal. CIZ1 is expressed in proliferating stem cells of the testis, but is notably down-regulated following commitment to differentiation. Significantly, CIZ1 is re-expressed at high levels in non-proliferative spermatocytes prior to meiotic division. Sequence analysis identifies at least seven alternatively spliced variants at this time, including a dominant cancer-associated form and a set of novel isoforms. Furthermore, we show that in these post-replicative cells CIZ1 interacts with the germ cell specific cyclin, A1, that has been implicated in DNA double-strand break repair. Consistent with this role, antibody depletion of CIZ1 reduces the capacity for testis extract to repair digested plasmid DNA in vitro. Together, the data imply novel post-replicative roles for CIZ1 in germ cell differentiation that may include meiotic recombination, a process intrinsic to genome stability and diversification.

KW - Alternative splicing

KW - Cancer

KW - CIZ1

KW - Cyclin A1

KW - Development

KW - Male germ cell

U2 - 10.1242/jcs.101097

DO - 10.1242/jcs.101097

M3 - Journal article

C2 - 22366453

VL - 125

SP - 2466

EP - 2477

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

ER -