The involvement of FANCM, FANCI, and checkpoint proteins in the interstrand DNA crosslink repair pathway is conserved in C. elegans

Kyong Yun Lee; Kee Yang Chung; Hyeon Sook Koo

doi:10.1016/j.dnarep.2009.12.018

The involvement of FANCM, FANCI, and checkpoint proteins in the interstrand DNA crosslink repair pathway is conserved in C. elegans

Kyong Yun Lee, Kee Yang Chung, Hyeon Sook Koo

Department of Biochemistry

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

20 Citations (Scopus)

Abstract

Fanconi anemia (FA) patients are specifically defective in the repair of interstrand DNA crosslinks (ICLs), a complex process involving at least 13 FA proteins and other repair/checkpoint proteins. Of the 13 FA proteins, FANCD1/BRCA2, FANCD2, and FANCJ were previously found to be functionally conserved in C. elegans. We have also identified C. elegans homologs of FANCM and FANCI, and determined their epistatic relationships with homologs of FANCD2, checkpoint proteins, and RAD51 upon DNA crosslinking. The counterparts of FANCM, FANCI, and three checkpoint proteins (RPA, ATR and CHK1) are required for focus formation and ubiquitination associated with FANCD2 in C. elegans. However, C. elegans FANCM affects neither RPA focus formation nor CHK1 phosphorylation induced by ICLs, unlike the reported role of human FANCM, which influences ATR-CHK1 signaling at stalled replication forks. Although focus formation by both FANCD2 and RAD51 requires ATR-CHK1 signaling, FANCD2 and RAD51 acted independently in the formation of their respective foci. Thus, the FANCD2 activation pathway involving FANCM, FANCI, and the checkpoint proteins is conserved in C. elegans but with distinct differences.

Original language	English
Pages (from-to)	374-382
Number of pages	9
Journal	DNA Repair
Volume	9
Issue number	4
DOIs	https://doi.org/10.1016/j.dnarep.2009.12.018
Publication status	Published - 2010 Apr 4

Bibliographical note

Funding Information:
We thank Dr. Yuji Kohara (National Institute of Genetics, Japan) for the EST clones. The C. elegans N2 strain was obtained from the C. elegans Genetics Center (St. Paul, MN), which is supported by the National Center for Research Resources. The fncm-1(tm3148), fcd-2(tm1298), and fnci-1(tm3081) strains were kindly provided by the National Bioresource Project (Japan). The monoclonal antibody against α-tubulin developed by Frankel and Nielsen was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. We appreciate comments from Kyungjae Myung (National Human Genome Research Institute, NIH, USA) and Anton Gartner (the University of Dundee, U.K.). Our work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) ( KRF-2007-313-C00508 ) and a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (no. 2009-0080247 ).

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.dnarep.2009.12.018

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title = "The involvement of FANCM, FANCI, and checkpoint proteins in the interstrand DNA crosslink repair pathway is conserved in C. elegans",

abstract = "Fanconi anemia (FA) patients are specifically defective in the repair of interstrand DNA crosslinks (ICLs), a complex process involving at least 13 FA proteins and other repair/checkpoint proteins. Of the 13 FA proteins, FANCD1/BRCA2, FANCD2, and FANCJ were previously found to be functionally conserved in C. elegans. We have also identified C. elegans homologs of FANCM and FANCI, and determined their epistatic relationships with homologs of FANCD2, checkpoint proteins, and RAD51 upon DNA crosslinking. The counterparts of FANCM, FANCI, and three checkpoint proteins (RPA, ATR and CHK1) are required for focus formation and ubiquitination associated with FANCD2 in C. elegans. However, C. elegans FANCM affects neither RPA focus formation nor CHK1 phosphorylation induced by ICLs, unlike the reported role of human FANCM, which influences ATR-CHK1 signaling at stalled replication forks. Although focus formation by both FANCD2 and RAD51 requires ATR-CHK1 signaling, FANCD2 and RAD51 acted independently in the formation of their respective foci. Thus, the FANCD2 activation pathway involving FANCM, FANCI, and the checkpoint proteins is conserved in C. elegans but with distinct differences.",

author = "Lee, {Kyong Yun} and Chung, {Kee Yang} and Koo, {Hyeon Sook}",

note = "Funding Information: We thank Dr. Yuji Kohara (National Institute of Genetics, Japan) for the EST clones. The C. elegans N2 strain was obtained from the C. elegans Genetics Center (St. Paul, MN), which is supported by the National Center for Research Resources. The fncm-1(tm3148), fcd-2(tm1298), and fnci-1(tm3081) strains were kindly provided by the National Bioresource Project (Japan). The monoclonal antibody against α-tubulin developed by Frankel and Nielsen was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. We appreciate comments from Kyungjae Myung (National Human Genome Research Institute, NIH, USA) and Anton Gartner (the University of Dundee, U.K.). Our work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) ( KRF-2007-313-C00508 ) and a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (no. 2009-0080247 ). ",

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doi = "10.1016/j.dnarep.2009.12.018",

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T1 - The involvement of FANCM, FANCI, and checkpoint proteins in the interstrand DNA crosslink repair pathway is conserved in C. elegans

AU - Lee, Kyong Yun

AU - Chung, Kee Yang

AU - Koo, Hyeon Sook

N1 - Funding Information: We thank Dr. Yuji Kohara (National Institute of Genetics, Japan) for the EST clones. The C. elegans N2 strain was obtained from the C. elegans Genetics Center (St. Paul, MN), which is supported by the National Center for Research Resources. The fncm-1(tm3148), fcd-2(tm1298), and fnci-1(tm3081) strains were kindly provided by the National Bioresource Project (Japan). The monoclonal antibody against α-tubulin developed by Frankel and Nielsen was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. We appreciate comments from Kyungjae Myung (National Human Genome Research Institute, NIH, USA) and Anton Gartner (the University of Dundee, U.K.). Our work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) ( KRF-2007-313-C00508 ) and a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (no. 2009-0080247 ).

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N2 - Fanconi anemia (FA) patients are specifically defective in the repair of interstrand DNA crosslinks (ICLs), a complex process involving at least 13 FA proteins and other repair/checkpoint proteins. Of the 13 FA proteins, FANCD1/BRCA2, FANCD2, and FANCJ were previously found to be functionally conserved in C. elegans. We have also identified C. elegans homologs of FANCM and FANCI, and determined their epistatic relationships with homologs of FANCD2, checkpoint proteins, and RAD51 upon DNA crosslinking. The counterparts of FANCM, FANCI, and three checkpoint proteins (RPA, ATR and CHK1) are required for focus formation and ubiquitination associated with FANCD2 in C. elegans. However, C. elegans FANCM affects neither RPA focus formation nor CHK1 phosphorylation induced by ICLs, unlike the reported role of human FANCM, which influences ATR-CHK1 signaling at stalled replication forks. Although focus formation by both FANCD2 and RAD51 requires ATR-CHK1 signaling, FANCD2 and RAD51 acted independently in the formation of their respective foci. Thus, the FANCD2 activation pathway involving FANCM, FANCI, and the checkpoint proteins is conserved in C. elegans but with distinct differences.

AB - Fanconi anemia (FA) patients are specifically defective in the repair of interstrand DNA crosslinks (ICLs), a complex process involving at least 13 FA proteins and other repair/checkpoint proteins. Of the 13 FA proteins, FANCD1/BRCA2, FANCD2, and FANCJ were previously found to be functionally conserved in C. elegans. We have also identified C. elegans homologs of FANCM and FANCI, and determined their epistatic relationships with homologs of FANCD2, checkpoint proteins, and RAD51 upon DNA crosslinking. The counterparts of FANCM, FANCI, and three checkpoint proteins (RPA, ATR and CHK1) are required for focus formation and ubiquitination associated with FANCD2 in C. elegans. However, C. elegans FANCM affects neither RPA focus formation nor CHK1 phosphorylation induced by ICLs, unlike the reported role of human FANCM, which influences ATR-CHK1 signaling at stalled replication forks. Although focus formation by both FANCD2 and RAD51 requires ATR-CHK1 signaling, FANCD2 and RAD51 acted independently in the formation of their respective foci. Thus, the FANCD2 activation pathway involving FANCM, FANCI, and the checkpoint proteins is conserved in C. elegans but with distinct differences.

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The involvement of FANCM, FANCI, and checkpoint proteins in the interstrand DNA crosslink repair pathway is conserved in C. elegans

Abstract

Bibliographical note

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