Phosphorylation of human DNA polymerase λ by the cyclin-dependent kinase Cdk2/cyclin A complex is modulated by its association with proliferating cell nuclear antigen

被引:39
作者
Frouin, I [1 ]
Toueille, M [1 ]
Ferrari, E [1 ]
Shevelev, I [1 ]
Hübscher, U [1 ]
机构
[1] Univ Zurich, Inst Vet Biochem & Mol Biol, CH-8057 Zurich, Switzerland
关键词
D O I
10.1093/nar/gki845
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
DNA polymerase (Pol) lambda is a member of the Pol X family and possesses four different enzymatic activities, being DNA polymerase, terminal transferase, deoxyribose phosphate lyase and polynucleotide synthetase, all localized in its C-terminal region. On the basis of its biochemical properties, Pol lambda has been implicated in various DNA repair pathways, such as abasic site translesion DNA synthesis, base excision repair and non-homologous end joining of double strand breaks. However, its role in vivo has not yet been elucidated. In addition, Pol lambda has been shown to interact with the replication clamp proliferating cell nuclear antigen (PCNA) in vitro and in vivo. In this work, we searched by affinity chromatography for novel partners and we identified the cyclin-dependent kinase Cdk2 as novel partner of Pol lambda. Pol lambda is phosphorylated in vitro by several Cdk/cyclin complexes, including Cdk2/cyclin A, in its prolineserine-rich domain. While the polymerase activity of Pol lambda was not affected by Cdk2/cyclin A phosphorylation, phosphorylation of Pol lambda was decreased by its interaction with PCNA. Finally, Pol lambda is also phosphorylated in vivo in human cells and this phosphorylation is modulated during the cell cycle.
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页码:5354 / 5361
页数:8
相关论文
共 36 条
  • [1] Aleem E, 2004, CELL CYCLE, V3, P35
  • [2] Ashley T, 2001, J CELL SCI, V114, P685
  • [3] Human DNA polymerases λ and β show different efficiencies of translesion DNA synthesis past abasic sites and alternative mechanisms for frameshift generation
    Blanca, G
    Villani, G
    Shevelev, I
    Ramadan, K
    Spadari, S
    Hübscher, U
    Maga, G
    [J]. BIOCHEMISTRY, 2004, 43 (36) : 11605 - 11615
  • [4] DNA polymerase λ protects mouse fibroblasts against oxidative DNA damage and is recruited to sites of DNA damage/repair
    Braithwaite, EK
    Kedar, PS
    Lan, L
    Polosina, YY
    Asagoshi, K
    Poltoratsky, VP
    Horton, JK
    Miller, H
    Teebor, GW
    Yasui, A
    Wilson, SH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (36) : 31641 - 31647
  • [5] DNA polymerase λ mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblasts
    Braithwaite, EK
    Prasad, R
    Shock, DD
    Hou, EW
    Beard, WA
    Wilson, SH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (18) : 18469 - 18475
  • [6] Identification of interaction partners and substrates of the cyclin A1-CDK2 complex
    Diederichs, S
    Bäumer, N
    Ji, P
    Metzelder, SK
    Idos, GE
    Cauvet, T
    Wang, WB
    Möller, M
    Pierschalski, S
    Gromoll, J
    Schrader, MG
    Koeffler, HP
    Berdel, WE
    Serve, H
    Müller-Tidow, C
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (32) : 33727 - 33741
  • [7] DNA polymerase λ can elongate on DNA substrates mimicking non-homologous end joining and interact with XRCC4-ligase IV complex
    Fan, W
    Wu, XM
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 323 (04) : 1328 - 1333
  • [8] Cell cycle-dependent phosphorylation of human DNA ligase I at the cyclin-dependent kinase sites
    Ferrari, G
    Rossi, R
    Arosio, D
    Vindigni, A
    Biamonti, G
    Montecucco, A
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (39) : 37761 - 37767
  • [9] Identification of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in human DNA polymerase λ -: A possible role in base excision repair
    García-Díaz, M
    Bebenek, K
    Kunkel, TA
    Blanco, L
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (37) : 34659 - 34663
  • [10] DNA polymerase lambda (Pol λ), a novel eukaryotic DNA polymerase with a potential role in meiosis
    García-Díaz, M
    Domínguez, O
    López-Fernández, LA
    de Lera, LT
    Saníger, ML
    Ruiz, JF
    Párraga, M
    García-Ortiz, MJ
    Kirchhoff, T
    del Mazo, J
    Bernad, A
    Blanco, L
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2000, 301 (04) : 851 - 867