MHF1-MHF2, a Histone-Fold-Containing Protein Complex, Participates in the Fanconi Anemia Pathway via FANCM

Thiyam Ramsing Singh; Dorina Saro; Abdullah Mahmood Ali; Xiao Feng Zheng; Chang hu Du; Michael W. Killen; Aristidis Sachpatzidis; Kebola Wahengbam; Andrew J. Pierce; Yong Xiong; Patrick Sung; Amom Ruhikanta Meetei

doi:10.1016/j.molcel.2010.01.036

MHF1-MHF2, a Histone-Fold-Containing Protein Complex, Participates in the Fanconi Anemia Pathway via FANCM

Thiyam Ramsing Singh, Dorina Saro, Abdullah Mahmood Ali, Xiao Feng Zheng, Chang hu Du, Michael W. Killen, Aristidis Sachpatzidis, Kebola Wahengbam, Andrew J. Pierce, Yong Xiong, Patrick Sung, Amom Ruhikanta Meetei

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

160 Scopus citations

Abstract

FANCM is a Fanconi anemia nuclear core complex protein required for the functional integrity of the FANC-BRCA pathway of DNA damage response and repair. Here we report the isolation and characterization of two histone-fold-containing FANCM-associated proteins, MHF1 and MHF2. We show that suppression of MHF1 expression results in (1) destabilization of FANCM and MHF2, (2) impairment of DNA damage-induced monoubiquitination and foci formation of FANCD2, (3) defective chromatin localization of FA nuclear core complex proteins, (4) elevated MMC-induced chromosome aberrations, and (5) sensitivity to MMC and camptothecin. We also provide biochemical evidence that MHF1 and MHF2 assemble into a heterodimer that binds DNA and enhances the DNA branch migration activity of FANCM. These findings reveal critical roles of the MHF1-MHF2 dimer in DNA damage repair and genome maintenance through FANCM.

Original language	English (US)
Pages (from-to)	879-886
Number of pages	8
Journal	Molecular Cell
Volume	37
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2010.01.036
State	Published - Mar 26 2010
Externally published	Yes

Keywords

DNA
PROTEINS

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2010.01.036

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@article{d1ce0660eba14565a2be957cbc0d433b,

title = "MHF1-MHF2, a Histone-Fold-Containing Protein Complex, Participates in the Fanconi Anemia Pathway via FANCM",

abstract = "FANCM is a Fanconi anemia nuclear core complex protein required for the functional integrity of the FANC-BRCA pathway of DNA damage response and repair. Here we report the isolation and characterization of two histone-fold-containing FANCM-associated proteins, MHF1 and MHF2. We show that suppression of MHF1 expression results in (1) destabilization of FANCM and MHF2, (2) impairment of DNA damage-induced monoubiquitination and foci formation of FANCD2, (3) defective chromatin localization of FA nuclear core complex proteins, (4) elevated MMC-induced chromosome aberrations, and (5) sensitivity to MMC and camptothecin. We also provide biochemical evidence that MHF1 and MHF2 assemble into a heterodimer that binds DNA and enhances the DNA branch migration activity of FANCM. These findings reveal critical roles of the MHF1-MHF2 dimer in DNA damage repair and genome maintenance through FANCM.",

keywords = "DNA, PROTEINS",

author = "Singh, {Thiyam Ramsing} and Dorina Saro and Ali, {Abdullah Mahmood} and Zheng, {Xiao Feng} and Du, {Chang hu} and Killen, {Michael W.} and Aristidis Sachpatzidis and Kebola Wahengbam and Pierce, {Andrew J.} and Yong Xiong and Patrick Sung and Meetei, {Amom Ruhikanta}",

note = "Funding Information: We are grateful to Drs. Weidong Wang and Stephen West for reagents and to Dongqing Liu for the preparation of FANCM baculoviruses. We thank the Cytogenetics Laboratory, Viral Vector Core, Fluorescent Activated Cell Analyzing, and Sorting Facility of Cincinnati Children's Research Foundation; and the Taplin Biological Mass Spectrometry Facility at Harvard Medical School for their excellent service. This work was supported by National Institutes of Health research grants ES015632, ES07061 (P.S.), and HL084082 (A.R.M); the Fanconi Anemia Research Fund (A.R.M.); and the American Society of Hematology Junior Faculty Award (A.R.M). ",

year = "2010",

month = mar,

day = "26",

doi = "10.1016/j.molcel.2010.01.036",

language = "English (US)",

volume = "37",

pages = "879--886",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - MHF1-MHF2, a Histone-Fold-Containing Protein Complex, Participates in the Fanconi Anemia Pathway via FANCM

AU - Singh, Thiyam Ramsing

AU - Saro, Dorina

AU - Ali, Abdullah Mahmood

AU - Zheng, Xiao Feng

AU - Du, Chang hu

AU - Killen, Michael W.

AU - Sachpatzidis, Aristidis

AU - Wahengbam, Kebola

AU - Pierce, Andrew J.

AU - Xiong, Yong

AU - Sung, Patrick

AU - Meetei, Amom Ruhikanta

N1 - Funding Information: We are grateful to Drs. Weidong Wang and Stephen West for reagents and to Dongqing Liu for the preparation of FANCM baculoviruses. We thank the Cytogenetics Laboratory, Viral Vector Core, Fluorescent Activated Cell Analyzing, and Sorting Facility of Cincinnati Children's Research Foundation; and the Taplin Biological Mass Spectrometry Facility at Harvard Medical School for their excellent service. This work was supported by National Institutes of Health research grants ES015632, ES07061 (P.S.), and HL084082 (A.R.M); the Fanconi Anemia Research Fund (A.R.M.); and the American Society of Hematology Junior Faculty Award (A.R.M).

PY - 2010/3/26

Y1 - 2010/3/26

N2 - FANCM is a Fanconi anemia nuclear core complex protein required for the functional integrity of the FANC-BRCA pathway of DNA damage response and repair. Here we report the isolation and characterization of two histone-fold-containing FANCM-associated proteins, MHF1 and MHF2. We show that suppression of MHF1 expression results in (1) destabilization of FANCM and MHF2, (2) impairment of DNA damage-induced monoubiquitination and foci formation of FANCD2, (3) defective chromatin localization of FA nuclear core complex proteins, (4) elevated MMC-induced chromosome aberrations, and (5) sensitivity to MMC and camptothecin. We also provide biochemical evidence that MHF1 and MHF2 assemble into a heterodimer that binds DNA and enhances the DNA branch migration activity of FANCM. These findings reveal critical roles of the MHF1-MHF2 dimer in DNA damage repair and genome maintenance through FANCM.

AB - FANCM is a Fanconi anemia nuclear core complex protein required for the functional integrity of the FANC-BRCA pathway of DNA damage response and repair. Here we report the isolation and characterization of two histone-fold-containing FANCM-associated proteins, MHF1 and MHF2. We show that suppression of MHF1 expression results in (1) destabilization of FANCM and MHF2, (2) impairment of DNA damage-induced monoubiquitination and foci formation of FANCD2, (3) defective chromatin localization of FA nuclear core complex proteins, (4) elevated MMC-induced chromosome aberrations, and (5) sensitivity to MMC and camptothecin. We also provide biochemical evidence that MHF1 and MHF2 assemble into a heterodimer that binds DNA and enhances the DNA branch migration activity of FANCM. These findings reveal critical roles of the MHF1-MHF2 dimer in DNA damage repair and genome maintenance through FANCM.

KW - DNA

KW - PROTEINS

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DO - 10.1016/j.molcel.2010.01.036

M3 - Article

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AN - SCOPUS:77949563363

SN - 1097-2765

VL - 37

SP - 879

EP - 886

JO - Molecular Cell

JF - Molecular Cell

IS - 6

ER -

MHF1-MHF2, a Histone-Fold-Containing Protein Complex, Participates in the Fanconi Anemia Pathway via FANCM

Abstract

Keywords

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