RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination

被引:78
作者
Doherty, KM
Sharma, S
Uzdilla, LA
Wilson, TM
Cui, S
Vindigni, A
Brosh, RM
机构
[1] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA
[2] Univ Maryland, Dept Radiat Oncol, Radiat Oncol Res Lab, Baltimore, MD 21201 USA
[3] Int Ctr Genet Engn & Biotechnol, I-34012 Trieste, Italy
关键词
D O I
10.1074/jbc.M500265200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Understanding the molecular and cellular functions of RecQ helicases has attracted considerable interest since several human diseases characterized by premature aging and/or cancer have been genetically linked to mutations in genes of the RecQ family. Although a human disease has not yet been genetically linked to a mutation in RECQ1, the prominent roles of RecQ helicases in the maintenance of genome stability suggest that RECQ1 helicase is likely to be important in vivo. To acquire a better understanding of RECQ1 cellular and molecular functions, we have investigated its protein interactions. Using a co-immunoprecipitation approach, we have identified several DNA repair factors that are associated with RECQ1 in vivo. Direct physical interaction of these repair factors with RECQ1 was confirmed with purified recombinant proteins. Importantly, RECQ1 stimulates the incision activity of human exonuclease 1 and the mismatch repair recognition complex MSH2/6 stimulates RECQ1 helicase activity. These protein interactions suggest a role of RECQ1 in a pathway involving mismatch repair factors. Regulation of genetic recombination, a proposed role for RecQ helicases, is supported by the identified RECQ1 protein interactions and is discussed.
引用
收藏
页码:28085 / 28094
页数:10
相关论文
共 55 条
[21]   RecQ helicases: Caretakers of the genome [J].
Hickson, ID .
NATURE REVIEWS CANCER, 2003, 3 (03) :169-178
[22]  
Johnson FB, 2000, CANCER RES, V60, P1162
[23]   RecQ helicases: multiple roles in genome maintenance [J].
Khakhar, RR ;
Cobb, JA ;
Bjergbaek, L ;
Hickson, ID ;
Gasser, SM .
TRENDS IN CELL BIOLOGY, 2003, 13 (09) :493-501
[24]   The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair [J].
Langland, G ;
Kordich, J ;
Creaney, J ;
Goss, KH ;
Lillard-Wetherell, K ;
Bebenek, K ;
Kunkel, TA ;
Groden, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (32) :30031-30035
[25]   The RAD2 domain of human exonuclease 1 exhibits 5′ to 3′ exonuclease and flap structure-specific endonuclease activities [J].
Lee, BI ;
Wilson, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (53) :37763-37769
[26]  
Lewis LK, 2002, GENETICS, V160, P49
[27]  
Mansour AA, 2001, GENETICS, V158, P77
[28]   EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Δ mutants [J].
Maringele, L ;
Lydall, D .
GENES & DEVELOPMENT, 2002, 16 (15) :1919-1933
[29]   EXO1 plays a role in generating type I and type II survivors in budding yeast [J].
Maringele, L ;
Lydall, D .
GENETICS, 2004, 166 (04) :1641-1649
[30]   Evidence for multiple cycles of strand invasion during repair of double-strand gaps in Drosophila [J].
McVey, M ;
Adams, M ;
Staeva-Vieira, E ;
Sekelsky, JJ .
GENETICS, 2004, 167 (02) :699-705