Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes

Amy E.Hanlon Newell; Yassmine M.N. Akkari; Yumi Torimaru; Andrew Rosenthal; Carol A. Reifsteck; Barbara Cox; Markus Grompe; Susan B. Olson

doi:10.1016/j.dnarep.2004.01.011

Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes

Amy E.Hanlon Newell
, Yassmine M.N. Akkari
, Yumi Torimaru
, Andrew Rosenthal
, Carol A. Reifsteck
, Barbara Cox
, Markus Grompe
, Susan B. Olson

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

29 Scopus citations

Abstract

Fanconi anemia (FA) and cells lacking functional BRCA1 and BRCA2 proteins are hypersensitive to interstrand crosslinking (ICL) agents and show increased numbers of chromosomal breaks and radials. Although radial formation has been used to diagnose FA for more than 30 years, there has been little analysis of these characteristic formations. In this study, radials were analyzed from FA-A and FA-G fibroblasts as well as normal and retrovirally-corrected FA-A fibroblasts treated with high doses of ICLs. Radials were found to only involve non-homologous chromosome interactions and to be distributed nearly randomly along the length of chromosomes. Sites on chromosomes that did show increased frequency of radial involvement did not correlate with known fragile sites or pericentric regions. Hybrid radials were observed between mouse and human chromosomes in human-mouse hybrid cells produced by microcell-mediated chromosome transfer of mouse chromosomes into human FA-A fibroblasts. Both X and Y chromosomes were notably not involved in radials. These observations suggest that ICL repair may involve short stretches of homology, resulting in aberrant radial formation in the absence of FA proteins.

Original language	English (US)
Pages (from-to)	535-542
Number of pages	8
Journal	DNA Repair
Volume	3
Issue number	5
DOIs	https://doi.org/10.1016/j.dnarep.2004.01.011
State	Published - May 4 2004

Funding

We thank Gary Sexton for assistance in statistical analysis, and Michael Brown, Helen Lawce, Eleanor Himoe, Mary Black, and Craig Davis for their technical expertise. We also thank R. Ellen Magenis, Matt Thayer, and Kevin McCabe for useful discussions. This work was supported by an NHLBI Program project grant PO1HL48546 to S.B.O., and a post-doctoral NIH Training Grant GM08796 to Y.M.N.A.

Funders	Funder number
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	GM08796
National Institute of Health National Heart, Lung, and Blood Institute	P01HL048546

Keywords

Chromosomes
Fanconi anemia
Interstrand crosslink

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.dnarep.2004.01.011

Cite this

@article{35c5b15a6ed74fd7bafa94255cb633ef,

title = "Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes",

abstract = "Fanconi anemia (FA) and cells lacking functional BRCA1 and BRCA2 proteins are hypersensitive to interstrand crosslinking (ICL) agents and show increased numbers of chromosomal breaks and radials. Although radial formation has been used to diagnose FA for more than 30 years, there has been little analysis of these characteristic formations. In this study, radials were analyzed from FA-A and FA-G fibroblasts as well as normal and retrovirally-corrected FA-A fibroblasts treated with high doses of ICLs. Radials were found to only involve non-homologous chromosome interactions and to be distributed nearly randomly along the length of chromosomes. Sites on chromosomes that did show increased frequency of radial involvement did not correlate with known fragile sites or pericentric regions. Hybrid radials were observed between mouse and human chromosomes in human-mouse hybrid cells produced by microcell-mediated chromosome transfer of mouse chromosomes into human FA-A fibroblasts. Both X and Y chromosomes were notably not involved in radials. These observations suggest that ICL repair may involve short stretches of homology, resulting in aberrant radial formation in the absence of FA proteins.",

keywords = "Chromosomes, Fanconi anemia, Interstrand crosslink",

author = "Newell, \{Amy E.Hanlon\} and Akkari, \{Yassmine M.N.\} and Yumi Torimaru and Andrew Rosenthal and Reifsteck, \{Carol A.\} and Barbara Cox and Markus Grompe and Olson, \{Susan B.\}",

note = "Funding Information: We thank Gary Sexton for assistance in statistical analysis, and Michael Brown, Helen Lawce, Eleanor Himoe, Mary Black, and Craig Davis for their technical expertise. We also thank R. Ellen Magenis, Matt Thayer, and Kevin McCabe for useful discussions. This work was supported by an NHLBI Program project grant PO1HL48546 to S.B.O., and a post-doctoral NIH Training Grant GM08796 to Y.M.N.A.",

year = "2004",

month = may,

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doi = "10.1016/j.dnarep.2004.01.011",

language = "English (US)",

volume = "3",

pages = "535--542",

journal = "DNA Repair",

issn = "1568-7864",

publisher = "Elsevier B.V.",

number = "5",

}

TY - JOUR

T1 - Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes

AU - Newell, Amy E.Hanlon

AU - Akkari, Yassmine M.N.

AU - Torimaru, Yumi

AU - Rosenthal, Andrew

AU - Reifsteck, Carol A.

AU - Cox, Barbara

AU - Grompe, Markus

AU - Olson, Susan B.

N1 - Funding Information: We thank Gary Sexton for assistance in statistical analysis, and Michael Brown, Helen Lawce, Eleanor Himoe, Mary Black, and Craig Davis for their technical expertise. We also thank R. Ellen Magenis, Matt Thayer, and Kevin McCabe for useful discussions. This work was supported by an NHLBI Program project grant PO1HL48546 to S.B.O., and a post-doctoral NIH Training Grant GM08796 to Y.M.N.A.

PY - 2004/5/4

Y1 - 2004/5/4

N2 - Fanconi anemia (FA) and cells lacking functional BRCA1 and BRCA2 proteins are hypersensitive to interstrand crosslinking (ICL) agents and show increased numbers of chromosomal breaks and radials. Although radial formation has been used to diagnose FA for more than 30 years, there has been little analysis of these characteristic formations. In this study, radials were analyzed from FA-A and FA-G fibroblasts as well as normal and retrovirally-corrected FA-A fibroblasts treated with high doses of ICLs. Radials were found to only involve non-homologous chromosome interactions and to be distributed nearly randomly along the length of chromosomes. Sites on chromosomes that did show increased frequency of radial involvement did not correlate with known fragile sites or pericentric regions. Hybrid radials were observed between mouse and human chromosomes in human-mouse hybrid cells produced by microcell-mediated chromosome transfer of mouse chromosomes into human FA-A fibroblasts. Both X and Y chromosomes were notably not involved in radials. These observations suggest that ICL repair may involve short stretches of homology, resulting in aberrant radial formation in the absence of FA proteins.

AB - Fanconi anemia (FA) and cells lacking functional BRCA1 and BRCA2 proteins are hypersensitive to interstrand crosslinking (ICL) agents and show increased numbers of chromosomal breaks and radials. Although radial formation has been used to diagnose FA for more than 30 years, there has been little analysis of these characteristic formations. In this study, radials were analyzed from FA-A and FA-G fibroblasts as well as normal and retrovirally-corrected FA-A fibroblasts treated with high doses of ICLs. Radials were found to only involve non-homologous chromosome interactions and to be distributed nearly randomly along the length of chromosomes. Sites on chromosomes that did show increased frequency of radial involvement did not correlate with known fragile sites or pericentric regions. Hybrid radials were observed between mouse and human chromosomes in human-mouse hybrid cells produced by microcell-mediated chromosome transfer of mouse chromosomes into human FA-A fibroblasts. Both X and Y chromosomes were notably not involved in radials. These observations suggest that ICL repair may involve short stretches of homology, resulting in aberrant radial formation in the absence of FA proteins.

KW - Chromosomes

KW - Fanconi anemia

KW - Interstrand crosslink

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UR - https://www.scopus.com/pages/publications/1842685189#tab=citedBy

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VL - 3

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EP - 542

JO - DNA Repair

JF - DNA Repair

IS - 5

ER -

Interstrand crosslink-induced radials form between non-homologous chromosomes, but are absent in sex chromosomes

Abstract

Funding

Keywords

ASJC Scopus subject areas

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