Recruitment of DNA Polymerase Eta by FANCD2 in the Early Response to DNA Damage 

Cell Cycle. 2013 Mar 1;12(5):803-9.

Dechen Fu1,3, Fred Duafalia Dudimah1, 3, Jun Zhang2, Anna Pickering1, Jayabal Paneerselvam1, Manikandan Palrasu1, Hong Wang2,4 and Peiwen Fei1*

1University of Hawaii Cancer Center (UHCC), University of Hawaii, Honolulu, HI 96813        

2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN55905

3These authors contributed equally to this work.

4Current address: Department of Gastroenterology, First Municipal People’s Hospital of Guangzhou, First Affiliated Hospital Sun Yat-Sen University, Guangzhou, China

*Correspondence to:
Peiwen Fei, M.D., Ph.D.
BSB Rm 222
651 ILALO Street
Honolulu, HI 96813
Telephone: 808-356-5786
Fax: 808-587-0742
Email: pfei@cc.hawaii.edu

 

Abstract

How Fanconi Anemia (FA) protein D2 (FANCD2) performs DNA damage repair remains largely elusive. We report here that translesion synthesis DNA polymerase (pol) eta is a novel mediator of FANCD2 function. We found that wild type (wt) FANCD2, not K561R (mt) FANCD2, can interact with pol eta. Upon DNA damage, the interaction of pol eta with FANCD2 occurs earlier than that with PCNA, which is in concert with our finding that FANCD2 monoubiquitination peaks at an earlier time point than that of PCNA monoubiquitination. FANCD2-null FA patient cells (PD20), carrying histone H2B-fused pol eta and wtFANCD2, respectively, show a similar tendency of low Mitomycin C (MMC) sensitivity, while cells transfected with empty vector as a control or pol eta alone demonstrate a similar high level of MMC sensitivity. It therefore appears that FANCD2 monoubiquitination plays a similar anchor role as histone to bind DNA in regulating pol eta. Collectively, our study indicates that, in the early phase of DNA damage response, FANCD2 plays crucial roles in recruiting pol eta to the sites of DNA damage for repair.

 

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