Download Gene Section POLH (polymerase (DNA direct), eta) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Mini Review
POLH (polymerase (DNA direct), eta)
Anne Stary, Alain Sarasin
Laboratory of Genetic Instability and Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue
guy Moquet, BP 8, 94801 Villejuif, France (AS, AS)
Published in Atlas Database: February 2001
Online updated version : http://AtlasGeneticsOncology.org/Genes/XPVID303.html
DOI: 10.4267/2042/37726
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2001 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Mutations
Other names: XP-V; RAD30A
HGNC (Hugo): POLH
Location: 6p21.1
Note: See also the deep insight on: Nucleotide Excision
Repair.
Germinal
DNA/RNA
Disease
Predisposition to skin cancer.
12 mutated sites involved in the XP variant syndrome.
Implicated in
Xeroderma pigmentosum, XP group V
Description
References
11 exons.
Of the 11 splice donor/acceptor sites, 10 contained
consensus GT/AG dinucleotides; only the splice donor
site in exon 11 (sequence CT) varied from the
consensus pattern.
The POLH gene lacked a TATA sequence in the region
upstream of the transcription-initiation site and the
upstream region was GC rich (76% in the sequence
between +1 and Ð270).
The first ATG codon for initiation of translation was
included in the second exon. Exon 11 contained the
termination codon followed by 661 bp of 3’untranslated sequence.
Lehmann AR, Kirk-Bell S, Arlett CF, Paterson MC, Lohman
PH, de Weerd-Kastelein EA, Bootsma D. Xeroderma
pigmentosum cells with normal levels of excision repair have a
defect in DNA synthesis after UV-irradiation. Proc Natl Acad
Sci U S A. 1975 Jan;72(1):219-23
D'Ambrosio SM, Setlow RB. Defective and enhanced
postreplication repair in classical and variant xeroderma
pigmentosum
cells
treated
with
N-acetoxy-2acetylaminofluorene. Cancer Res. 1978 Apr;38(4):1147-53
Lehmann AR. The relationship between pyrimidine dimers and
replicating DNA in UV-irradiated human fibroblasts. Nucleic
Acids Res. 1979 Dec 11;7(7):1901-12
Minka DF, Nath J. Cytological evidence for DNA chain
elongation after UV irradiation in the S phase. Biochem Genet.
1981 Apr;19(3-4):199-210
Protein
Function
Cordeiro-Stone M, Boyer JC, Smith BA, Kaufmann WK.
Xeroderma pigmentosum variant and normal fibroblasts show
the same response to the inhibition of DNA replication by
benzo[a]pyrene-diol-epoxide-I.
Carcinogenesis.
1986
Oct;7(10):1783-6
The POLH gene encodes DNA polymerase h, which
catalyzes the translesion synthesis past a cis-syn T-T
pyrimidine dimer, one of the major DNA
photoproducts induced by UV light.
McCormick JJ, Kateley-Kohler S, Watanabe M, Maher VM.
Abnormal sensitivity of human fibroblasts from xeroderma
pigmentosum variants to transformation to anchorage
independence by ultraviolet radiation. Cancer Res. 1986
Feb;46(2):489-92
Description
713 amino acids.
Homology
Boyer JC, Kaufmann WK, Brylawski BP, Cordeiro-Stone M.
Defective postreplication repair in xeroderma pigmentosum
variant fibroblasts. Cancer Res. 1990 May 1;50(9):2593-8
mXPV: 80.3% amino acids identity and 86.9%
similarity.
Atlas Genet Cytogenet Oncol Haematol. 2001; 5(2)
98
POLH (polymerase (DNA direct), eta)
Stary A, Sarasin A
Griffiths TD, Ling SY. Effect of UV light on DNA chain growth
and replicon initiation in xeroderma pigmentosum variant cells.
Mutagenesis. 1991 Jul;6(4):247-51
Masutani C, Araki M, Yamada A, Kusumoto R, Nogimori T,
Maekawa T, Iwai S, Hanaoka F. Xeroderma pigmentosum
variant (XP-V) correcting protein from HeLa cells has a
thymine dimer bypass DNA polymerase activity. EMBO J. 1999
Jun 15;18(12):3491-501
Wang YC, Maher VM, McCormick JJ. Xeroderma
pigmentosum variant cells are less likely than normal cells to
incorporate dAMP opposite photoproducts during replication of
UV-irradiated plasmids. Proc Natl Acad Sci U S A. 1991 Sep
1;88(17):7810-4
Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M,
Yuasa M, Araki M, Iwai S, Takio K, Hanaoka F. The XPV
(xeroderma pigmentosum variant) gene encodes human DNA
polymerase. Nature. 1999 Jun 17;399(6737):700-4
Misra RR, Vos JM. Defective replication of psoralen adducts
detected at the gene-specific level in xeroderma pigmentosum
variant cells. Mol Cell Biol. 1993 Feb;13(2):1002-12
McGregor WG, Wei D, Maher VM, McCormick JJ. Abnormal,
error-prone bypass of photoproducts by xeroderma
pigmentosum variant cell extracts results in extreme strand
bias for the kinds of mutations induced by UV light. Mol Cell
Biol. 1999 Jan;19(1):147-54
Wang YC, Maher VM, Mitchell DL, McCormick JJ. Evidence
from mutation spectra that the UV hypermutability of
xeroderma pigmentosum variant cells reflects abnormal, errorprone replication on a template containing photoproducts. Mol
Cell Biol. 1993 Jul;13(7):4276-83
Goodman MF, Tippin B. Sloppier copier DNA polymerases
involved in genome repair. Curr Opin Genet Dev. 2000
Apr;10(2):162-8
Waters HL, Seetharam S, Seidman MM, Kraemer KH.
Ultraviolet hypermutability of a shuttle vector propagated in
xeroderma pigmentosum variant cells. J Invest Dermatol. 1993
Nov;101(5):744-8
Haracska L, Yu SL, Johnson RE, Prakash L, Prakash S.
Efficient and accurate replication in the presence of 7,8dihydro-8-oxoguanine by DNA polymerase eta. Nat Genet.
2000 Aug;25(4):458-61
Fujikawa K, Ayaki H, Ishizaki K, Takatera H, Matsuo S, Iizuka
H, Koizumi H, Ikenaga M. Assignment of six patients with
xeroderma pigmentosum in Hokkaido area to a variant form. J
Radiat Res (Tokyo). 1994 Sep;35(3):168-78
Johnson RE, Washington MT, Prakash S, Prakash L. Fidelity
of human DNA polymerase eta. J Biol Chem. 2000 Mar
17;275(11):7447-50
King SA, Wilson SJ, Farber RA, Kaufmann WK, CordeiroStone M. Xeroderma pigmentosum variant: generation and
characterization of fibroblastic cell lines transformed with SV40
large T antigen. Exp Cell Res. 1995 Mar;217(1):100-8
Limoli CL, Giedzinski E, Morgan WF, Cleaver JE. Polymerase
eta deficiency in the xeroderma pigmentosum variant uncovers
an overlap between the S phase checkpoint and double-strand
break repair. Proc Natl Acad Sci U S A. 2000 Jul
5;97(14):7939-46
Mitchell DL, Cleaver JE, Lowery MP, Hewitt RR. Induction and
repair of (6-4) photoproducts in normal human and xeroderma
pigmentosum variant cells during the cell cycle. Mutat Res.
1995 Nov;337(3):161-7
Masutani C, Kusumoto R, Iwai S, Hanaoka F. Mechanisms of
accurate translesion synthesis by human DNA polymerase eta.
EMBO J. 2000 Jun 15;19(12):3100-9
Tung BS, McGregor WG, Wang YC, Maher VM, McCormick
JJ. Comparison of the rate of excision of major UV
photoproducts in the strands of the human HPRT gene of
normal and xeroderma pigmentosum variant cells. Mutat Res.
1996 Jan 2;362(1):65-74
Matsuda T, Bebenek K, Masutani C, Hanaoka F, Kunkel TA.
Low fidelity DNA synthesis by human DNA polymerase-eta.
Nature. 2000 Apr 27;404(6781):1011-3
Yamada A, Masutani C, Iwai S, Hanaoka F. Complementation
of defective translesion synthesis and UV light sensitivity in
xeroderma pigmentosum variant cells by human and mouse
DNA polymerase eta. Nucleic Acids Res. 2000 Jul
1;28(13):2473-80
Ensch-Simon I, Burgers PM, Taylor JS. Bypass of a sitespecific cis-Syn thymine dimer in an SV40 vector during in vitro
replication by HeLa and XPV cell-free extracts. Biochemistry.
1998 Jun 2;37(22):8218-26
Yuasa M, Masutani C, Eki T, Hanaoka F. Genomic structure,
chromosomal localization and identification of mutations in the
xeroderma pigmentosum variant (XPV) gene. Oncogene. 2000
Sep 28;19(41):4721-8
Svoboda DL, Briley LP, Vos JM. Defective bypass replication
of a leading strand cyclobutane thymine dimer in xeroderma
pigmentosum variant cell extracts. Cancer Res. 1998 Jun
1;58(11):2445-8
Zhang Y, Yuan F, Wu X, Rechkoblit O, Taylor JS, Geacintov
NE, Wang Z. Error-prone lesion bypass by human DNA
polymerase eta. Nucleic Acids Res. 2000 Dec 1;28(23):471724
Cleaver JE, Afzal V, Feeney L, McDowell M, Sadinski W,
Volpe JP, Busch DB, Coleman DM, Ziffer DW, Yu Y,
Nagasawa H, Little JB. Increased ultraviolet sensitivity and
chromosomal instability related to P53 function in the
xeroderma pigmentosum variant. Cancer Res. 1999 Mar
1;59(5):1102-8
Bebenek K, Matsuda T, Masutani C ,et al. Proofreading of
DNA polymerase eta-dependent replication errors. J Biol
Chem. 2001 Jan 26;276(4):2317-20
Cordonnier AM, Fuchs RP. Replication of damaged DNA:
molecular defect in xeroderma pigmentosum variant cells.
Mutat Res. 1999 Oct 22;435(2):111-9
Haracska L, Washington MT, Prakash S, Prakash L. Inefficient
bypass of an abasic site by DNA polymerase eta. J Biol Chem.
2001 Mar 2;276(9):6861-6
Cordonnier AM, Lehmann AR, Fuchs RP. Impaired translesion
synthesis in xeroderma pigmentosum variant extracts. Mol Cell
Biol. 1999 Mar;19(3):2206-11
This article should be referenced as such:
Stary A, Sarasin A. POLH (polymerase (DNA direct), eta).
Atlas Genet Cytogenet Oncol Haematol. 2001; 5(2):98-99.
Johnson RE, Kondratick CM, Prakash S, Prakash L. hRAD30
mutations in the variant form of xeroderma pigmentosum.
Science. 1999 Jul 9;285(5425):263-5
Atlas Genet Cytogenet Oncol Haematol. 2001; 5(2)
99