2010 Fiscal Year Final Research Report
Characterization of new identified novel human AP endonuclease
| Project/Area Number |
20510047
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Risk sciences of radiation/Chemicals
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Keywords | AP endonuclease / PARP1 / base excision repair (BER) / single strand break repair (SSBR) |
|---|
| Research Abstract |
DUF2228 is a functionally unknown, conserved protein family distributed from worm to vertebrate including human. In insect and a part of worm DUF2228 protein has an additional domain containing a CYR motif (C2H2 zinc finger motif)in the N-terminal region. Since CYR motif was first identified in the human repair protein, PALF (ALPF), and found in various proteins of DNA metabolism, such as DNA repair and the DNA damage checkpoint, at their N-or C-termini, we hypothesized that DUF2228 family proteins have also DNA metabolism related functions. We isolated cDNA of Drosophila CG1218-PA and human C4orf27(APNX)belonging to DUF2228 and characterized these proteins. Here we show that ; 1)a Drosophila CG1218-PA protein accumulates at DNA damaged site in a poly-ADP-ribose-dependent manner. 2)Human APNX protein that lacks a CYR motif forms a hetero dimmer with PARP1 and accumulates at DNA damaged site in a PARP1-dependent manner. 3)CG1218-PA and APNX possess endo-and exonuclease activities against abasic site. 4)Suppression of the expression of APNX using siRNA in HeLa cells provided the cells with sensitivity to methyl methane sulfonate, which produces methylated bases leading to single-strand breaks. These data suggest that DUF2228 protein CG1218-PA and APNX play important roles in the repair of DNA base damage and single-strand breaks.
|
-
[Journal Article] CAMP (C13orf8, ZNF828)is a novel regulator of kinetochore-microtubule attachment.2011
Author(s)
Itoh, G, Kanno, S, Uchida, K, S, K, Chiba, S, Sugino, S, Watanabe, K, Mizuno, K, Yasui, A, Hirota, T, and Tanaka, K.
-
Journal Title
EMBO J
Volume: 30(1)
Pages: 130-44
DOI
Peer Reviewed
-
-
-
