POLH (polymerase (DNA direct), eta)

2001-02-01 Anne Stary , Alain Sarasin Affiliation

Laboratory of Genetic Instability, Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue guy Moquet, BP 8, 94801 VILLEJUIF, France

Identity

HGNC

POLH

LOCATION

6p21.1

LOCUSID

5429

ALIAS

RAD30,RAD30A,XP-V,XPV

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

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 270).

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

Proteins

Function

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

Homology

mXPV: 80.3% amino acids identity and 86.9% similarity

Mutations

Germinal

12 mutated sites involved in the XP variant syndrome

Implicated in

Entity name

xeroderma pigmentosum, XP group V

Disease

predisposition to skin cancer

Article Bibliography

Pubmed ID	Last Year	Title	Authors
11113111	2001	Proofreading of DNA polymerase eta-dependent replication errors.	Bebenek K et al
2109654	1990	Defective postreplication repair in xeroderma pigmentosum variant fibroblasts.	Boyer JC et al
10070969	1999	Increased ultraviolet sensitivity and chromosomal instability related to P53 function in the xeroderma pigmentosum variant.	Cleaver JE et al
3093115	1986	Xeroderma pigmentosum variant and normal fibroblasts show the same response to the inhibition of DNA replication by benzo[a]pyrene-diol-epoxide-I.	Cordeiro-Stone M et al
10022907	1999	Impaired translesion synthesis in xeroderma pigmentosum variant extracts.	Cordonnier AM et al
639041	1978	Defective and enhanced postreplication repair in classical and variant xeroderma pigmentosum cells treated with N-acetoxy-2-acetylaminofluorene.	D'Ambrosio SM et al
9609718	1998	Bypass of a site-specific cis-Syn thymine dimer in an SV40 vector during in vitro replication by HeLa and XPV cell-free extracts.	Ensch-Simon I et al
7830260	1994	Assignment of six patients with xeroderma pigmentosum in Hokkaido area to a variant form.	Fujikawa K et al
10753775	2000	Sloppier copier DNA polymerases involved in genome repair.	Goodman MF et al
1943714	1991	Effect of UV light on DNA chain growth and replicon initiation in xeroderma pigmentosum variant cells.	Griffiths TD et al
11106652	2001	Inefficient bypass of an abasic site by DNA polymerase eta.	Haracska L et al
10398605	1999	hRAD30 mutations in the variant form of xeroderma pigmentosum.	Johnson RE et al
7867708	1995	Xeroderma pigmentosum variant: generation and characterization of fibroblastic cell lines transformed with SV40 large T antigen.	King SA et al
231765	1979	The relationship between pyrimidine dimers and replicating DNA in UV-irradiated human fibroblasts.	Lehmann AR et al
1054497	1975	Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation.	Lehmann AR et al
10859352	2000	Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.	Limoli CL et al
10369688	1999	Xeroderma pigmentosum variant (XP-V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity.	Masutani C et al
10801132	2000	Low fidelity DNA synthesis by human DNA polymerase-eta.	Matsuda T et al
3940626	1986	Abnormal sensitivity of human fibroblasts from xeroderma pigmentosum variants to transformation to anchorage independence by ultraviolet radiation.	McCormick JJ et al
9858539	1999	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.	McGregor WG et al
7247930	1981	Cytological evidence for DNA chain elongation after UV irradiation in the S phase.	Minka DF et al
8423773	1993	Defective replication of psoralen adducts detected at the gene-specific level in xeroderma pigmentosum variant cells.	Misra RR et al
7491119	1995	Induction and repair of (6-4) photoproducts in normal human and xeroderma pigmentosum variant cells during the cell cycle.	Mitchell DL et al
9622087	1998	Defective bypass replication of a leading strand cyclobutane thymine dimer in xeroderma pigmentosum variant cell extracts.	Svoboda DL et al
8538650	1996	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.	Tung BS et al
1652764	1991	Xeroderma pigmentosum variant cells are less likely than normal cells to incorporate dAMP opposite photoproducts during replication of UV-irradiated plasmids.	Wang YC et al
8228338	1993	Ultraviolet hypermutability of a shuttle vector propagated in xeroderma pigmentosum variant cells.	Waters HL et al
10871396	2000	Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase eta.	Yamada A et al
11032022	2000	Genomic structure, chromosomal localization and identification of mutations in the xeroderma pigmentosum variant (XPV) gene.	Yuasa M et al
11095682	2000	Error-prone lesion bypass by human DNA polymerase eta.	Zhang Y et al

Other Information

Locus ID:

NCBI: 5429
MIM: 603968
HGNC: 9181
Ensembl: ENSG00000170734

Variants:

dbSNP: 5429
ClinVar: 5429
TCGA: ENSG00000170734
COSMIC: POLH

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000170734	ENST00000372226	Q9Y253
ENSG00000170734	ENST00000372236	Q9Y253
ENSG00000170734	ENST00000372236	A0A024RD62
ENSG00000170734	ENST00000443535	Q5JTF2

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Fanconi anemia pathway	KEGG	ko03460
Fanconi anemia pathway	KEGG	hsa03460
DNA Repair	REACTOME	R-HSA-73894
DNA Damage Bypass	REACTOME	R-HSA-73893
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	REACTOME	R-HSA-110313
Translesion Synthesis by POLH	REACTOME	R-HSA-110320
Termination of translesion DNA synthesis	REACTOME	R-HSA-5656169
DNA Double-Strand Break Repair	REACTOME	R-HSA-5693532
Homology Directed Repair	REACTOME	R-HSA-5693538
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)	REACTOME	R-HSA-5693567
HDR through Homologous Recombination (HRR)	REACTOME	R-HSA-5685942
Platinum drug resistance	KEGG	ko01524
Platinum drug resistance	KEGG	hsa01524

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37984186	2024	The accurate bypass of pyrimidine dimers by DNA polymerase eta contributes to ultraviolet-induced mutagenesis.	1
37984186	2024	The accurate bypass of pyrimidine dimers by DNA polymerase eta contributes to ultraviolet-induced mutagenesis.	1
36702254	2023	Primer terminal ribonucleotide alters the active site dynamics of DNA polymerase η and reduces DNA synthesis fidelity.	2
36758800	2023	Human DNA polymerase η promotes RNA-templated error-free repair of DNA double-strand breaks.	7
37129084	2023	Mutagenic incorporation of inosine into DNA via T:I mismatch formation by human DNA polymerase eta (polη).	2
37468099	2023	The peroxidation-derived DNA adduct, 6-oxo-M(1)dG, is a strong block to replication by human DNA polymerase η.	1
36702254	2023	Primer terminal ribonucleotide alters the active site dynamics of DNA polymerase η and reduces DNA synthesis fidelity.	2
36758800	2023	Human DNA polymerase η promotes RNA-templated error-free repair of DNA double-strand breaks.	7
37129084	2023	Mutagenic incorporation of inosine into DNA via T:I mismatch formation by human DNA polymerase eta (polη).	2
37468099	2023	The peroxidation-derived DNA adduct, 6-oxo-M(1)dG, is a strong block to replication by human DNA polymerase η.	1
34871863	2022	Incorporation of 5',8-cyclo-2'deoxyadenosines by DNA repair polymerases via base excision repair.	3
35328096	2022	Identification of Frameshift Variants in POLH Gene Causing Xeroderma Pigmentosum in Two Consanguineous Pakistani Families.	0
35952573	2022	Current state of knowledge of human DNA polymerase eta protein structure and disease-causing mutations.	6
34871863	2022	Incorporation of 5',8-cyclo-2'deoxyadenosines by DNA repair polymerases via base excision repair.	3
35328096	2022	Identification of Frameshift Variants in POLH Gene Causing Xeroderma Pigmentosum in Two Consanguineous Pakistani Families.	0

Citation

Anne Stary ; Alain Sarasin

POLH (polymerase (DNA direct), eta)

Atlas Genet Cytogenet Oncol Haematol. 2001-02-01

Online version: http://atlasgeneticsoncology.org/gene/303