Localisation of human Y-family DNA polymerase κ:: relationship to PCNA foci

被引:64
作者
Ogi, T [1 ]
Kannouche, P [1 ]
Lehmann, AR [1 ]
机构
[1] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RR, E Sussex, England
关键词
DNA polymerase; PCNA; replication foci; translesion synthesis; UV irradiation;
D O I
10.1242/jcs.01603
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
DNA polymerases of the Y-family are involved in translesion DNA synthesis past different types of DNA damage. Previous work has shown that DNA polymerases eta and iota are localised in replication factories during S phase, where they colocalise one-to-one with PCNA. Cells with factories containing these polymerases accumulate after treatment with DNA damaging agents because replication forks are stalled at sites of damage. We now show that DNA polymerase kappa (polkappa) has a different localisation pattern. Although, like the other Y-family polymerases, it is exclusively localised in the nucleus, polkappa is found in replication foci in only a small proportion of S-phase cells. It does not colocalise in those foci with proliferating cell nuclear antigen (PCNA) in the majority of cells. This reduced number of cells with polkappa foci, when compared with those containing poleta foci, is observed both in untreated cells and in cells treated with hydroxyurea, UV irradiation or benzo[a]pyrene. The C-terminal 97 amino acids of polkappa are sufficient for this limited localisation into nuclear foci, and include a C2HC zinc finger, bipartite nuclear localisation signal and putative PCNA binding site.
引用
收藏
页码:129 / 136
页数:8
相关论文
共 31 条
[1]   Localisation of human DNA polymerase κ to replication foci [J].
Bergoglio, V ;
Bavoux, C ;
Verbiest, V ;
Hoffmann, JS ;
Cazaux, C .
JOURNAL OF CELL SCIENCE, 2002, 115 (23) :4413-4418
[2]   Molecular analysis of mutations in DNA polymerase η in xeroderma pigmentosum-variant patients [J].
Broughton, BC ;
Cordonnier, A ;
Kleijer, WJ ;
Jaspers, NGJ ;
Fawcett, H ;
Raams, A ;
Garritsen, VH ;
Stary, A ;
Avril, MF ;
Boudsocq, F ;
Masutani, C ;
Hanaoka, F ;
Fuchs, RP ;
Sarasin, A ;
Lehmann, AR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (02) :815-820
[3]   Preferential misincorporation of purine nucleotides by human DNA polymerase η opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts [J].
Chiapperino, D ;
Kroth, H ;
Kramarczuk, IH ;
Sayer, JM ;
Masutani, C ;
Hanaoka, F ;
Jerina, DM ;
Cheh, AM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (14) :11765-11771
[4]   Human DNA polymerase κ bypasses and extends beyond thymine glycols during translesion synthesis in vitro, preferentially incorporating correct nucleotides [J].
Fischhaber, PL ;
Gerlach, VL ;
Feaver, WJ ;
Hatahet, Z ;
Wallace, SS ;
Friedberg, EC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (40) :37604-37611
[5]   Human and mouse homologs of Escherichia coli DinB (DNA polymerase IV), members of the UmuC/DinB superfamily [J].
Gerlach, VL ;
Aravind, L ;
Gotway, G ;
Schultz, RA ;
Koonin, EV ;
Friedberg, EC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (21) :11922-11927
[6]   Translesion synthesis by yeast DNA polymerase ζ from templates containing lesions of ultraviolet radiation and acetylaminofluorene [J].
Guo, DY ;
Wu, XH ;
Rajpal, DK ;
Taylor, JS ;
Wang, ZG .
NUCLEIC ACIDS RESEARCH, 2001, 29 (13) :2875-2883
[7]   Stimulation of DNA synthesis activity of human DNA polymerase κ by PCNA [J].
Haracska, L ;
Unk, I ;
Johnson, RE ;
Phillips, BB ;
Hurwitz, J ;
Prakash, L ;
Prakash, S .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (03) :784-791
[8]   Action of DNA repair endonuclease ERCC1/XPF in living cells [J].
Houtsmuller, AB ;
Rademakers, S ;
Nigg, AL ;
Hoogstraten, D ;
Hoeijmakers, JHJ ;
Vermeulen, W .
SCIENCE, 1999, 284 (5416) :958-961
[9]   Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions [J].
Johnson, RE ;
Washington, MT ;
Haracska, L ;
Prakash, S ;
Prakash, L .
NATURE, 2000, 406 (6799) :1015-1019
[10]   hRAD30 mutations in the variant form of xeroderma pigmentosum [J].
Johnson, RE ;
Kondratick, CM ;
Prakash, S ;
Prakash, L .
SCIENCE, 1999, 285 (5425) :263-265