POLQ

Official Full Name

DNA polymerase theta

Organism

Homo sapiens

Gene ID

10721

Background

Enables several functions, including catalytic activity, acting on DNA; identical protein binding activity; and magnesium ion binding activity. Involved in DNA metabolic process; negative regulation of double-strand break repair via homologous recombination; and protein homooligomerization. Located in Golgi apparatus; cytosol; and nucleoplasm. Is active in mitochondrial nucleoid; nucleus; and site of double-strand break. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

PRO0327

Cat.No.	Product Name	Price
CSC-DC012079	Panoply™ Human POLK Knockdown Stable Cell Line	Inquiry
CSC-DC012083	Panoply™ Human POLQ Knockdown Stable Cell Line	Inquiry
CSC-SC012079	Panoply™ Human POLK Over-expressing Stable Cell Line	Inquiry
CSC-SC012083	Panoply™ Human POLQ Over-expressing Stable Cell Line	Inquiry
CSC-RT0780	Human POLK Knockout Cell Line-HeLa	Inquiry

Cat.No.	Product Name	Price
AD12569Z	Human POLK adenoviral particles	Inquiry
LV22197L	human POLK (NM_016218) lentivirus particles	Inquiry
LV22202L	human POLQ (NM_199420) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH379312	shRNA set against Mouse POLQ (NM_029977.2)	Inquiry
SHH379260	shRNA set against Human POLK (NM_016218.2)	Inquiry
SHH379264	shRNA set against Mouse POLK (NM_012048.2)	Inquiry
SHH379268	shRNA set against Rat POLK (NM_138516.1)	Inquiry
SHH379308	shRNA set against Human POLQ (NM_199420.3)	Inquiry
SHH379316	shRNA set against Rat POLQ (NM_001105878.1)	Inquiry
SHW004700	shRNA set against Chicken POLK (NM_204183)	Inquiry

Cat.No.	Product Name	Price
CDCB166175	Chicken POLK ORF Clone (NM_204183)	Inquiry
MiUTR1M-09395	POLK miRNA 3'UTR clone	Inquiry
MiUTR1H-08069	POLQ miRNA 3'UTR clone	Inquiry
CDFR014222	Rat Polk cDNA Clone(NM_138516.1)	Inquiry
CDFR005605	Rat Polq cDNA Clone(NM_001105878.1)	Inquiry
CDFL010531	Mouse Polk cDNA Clone(NM_012048.2)	Inquiry
CDFG019843	Mouse Polq cDNA Clone(NM_001159369.1)	Inquiry
MiUTR3H-07857	POLK miRNA 3'UTR clone	Inquiry
SKO0684	POLK Validated sgRNA vector	Inquiry
CDCR263271	Mouse Polq ORF Clone(NM_029977.2)	Inquiry
CDCH065828	Mouse Polk ORF clone (NM_012048.2)	Inquiry
CDCB186543	Rabbit POLK ORF clone (XM_002723024.2)	Inquiry
CDCS414215	Human POLK ORF Clone (BC050718)	Inquiry
CDCR238517	Mouse Polq ORF Clone(NM_001159369.1)	Inquiry
CDCH065813	human POLQ ORF clone (NM_199420.3)	Inquiry
CDCB192507	Rabbit POLQ ORF clone (XM_002716640.2)	Inquiry
CDCR372524	Rat Polq ORF Clone(NM_001105878.1)	Inquiry
CDCR381269	Rat Polk ORF Clone(NM_138516.1)	Inquiry

Detailed Information

The POLQ gene encodes DNA polymerase θ, a unique member of the A-family DNA polymerases. Unlike the primary replicative polymerases, POLQ is evolutionarily ancient and exhibits an unusual structural fusion: it contains a central polymerase domain and an N-terminal superfamily 2 helicase-like domain. Such a combination is rare among eukaryotic DNA polymerases. POLQ is located on human chromosome 3q13.33 and primarily localizes to the cell nucleus, with pronounced enrichment at DNA double-strand break (DSB) sites, highlighting its central role in DNA damage response. POLQ expression varies across tissues and is frequently upregulated in various cancers, correlating with genome instability and reliance on specific DNA repair pathways. Mechanistically, POLQ is characterized by low fidelity, lacking the proofreading activity present in replicative polymerases, which contributes to its specialized role in DNA repair.

Biological Significance

POLQ plays a dominant role in a specialized form of non-homologous end joining known as microhomology-mediated end joining (MMEJ), a key pathway for repairing DNA double-strand breaks (DSBs). DSBs are among the most lethal forms of DNA damage, and cells use two main repair mechanisms: high-fidelity homologous recombination (HR) and error-prone non-homologous end joining (NHEJ). MMEJ, a variant of NHEJ, relies on short stretches of microhomology exposed at break ends to initiate repair. POLQ is central to this pathway. Its helicase-like domain displaces replication protein A (RPA) from single-stranded DNA, clearing the way for microhomology pairing and simultaneously suppressing RAD51 loading, thereby inhibiting HR and channeling repair toward MMEJ. POLQ's polymerase domain then extends the annealed ends in an error-prone manner, completing the ligation of broken DNA strands.

Figure 1. The pol domain of pol catalyzes multiple DNA-modifying activities. (Zahn KE, et al., 2021)

This process is inherently mutagenic, often causing deletions and chromosomal rearrangements such as telomere fusions, contributing to genomic instability. Nevertheless, MMEJ is indispensable under certain physiological contexts, such as during mitosis, when HR is suppressed by cell cycle constraints. POLQ also contributes to somatic hypermutation of immunoglobulin genes, where its low-fidelity synthesis introduces point mutations beneficial for antibody diversity. Overall, POLQ's dual role-promoting genomic instability yet maintaining chromosomal integrity under specific conditions-underpins its complex contribution to cancer biology.

Clinical Relevance

POLQ has emerged as a clinically significant target, particularly in oncology, due to its potential for synthetic lethality strategies. Synthetic lethality occurs when simultaneous loss of two genes leads to cell death, while loss of either alone does not. Tumors deficient in homologous recombination (HR), such as those with BRCA1 or BRCA2 mutations in breast, ovarian, and prostate cancers, rely heavily on POLQ-mediated MMEJ to repair persistent DSBs. Specific inhibition of POLQ in these HR-deficient cancers disables their backup repair pathway, leading to accumulation of irreparable DNA damage and apoptosis, while sparing normal cells with intact HR.

These findings have driven the development of POLQ inhibitors. Preclinical studies have demonstrated that small-molecule POLQ inhibitors selectively kill HR-deficient tumor cells and show potent anti-tumor activity in animal models, often synergizing with or overcoming resistance to PARP inhibitors. POLQ's relatively low expression in normal tissues suggests a favorable therapeutic window and reduced toxicity. In addition to serving as a therapeutic target, high POLQ expression in tumors may serve as a biomarker for HR deficiency and genomic instability, helping to identify patients likely to benefit from POLQ-targeted therapies. POLQ-mediated repair is also implicated in resistance to certain chemotherapies, indicating that combining POLQ inhibitors with existing treatments could overcome drug resistance. Overall, POLQ represents a critical node linking genomic instability to cancer cell survival and a promising target for next-generation DNA damage response therapies.

References

Ceccaldi R, Liu JC, Amunugama R, et al. Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair. Nature. 2015;518(7538):258–262.
Zhou J, Gelot C, Pantelidou C, et al. A first-in-class polymerase theta inhibitor selectively targets homologous-recombination-deficient tumors. Nat Cancer. 2021;2(6):598–610.
Zahn KE, Jensen RB. Polymerase θ Coordinates Multiple Intrinsic Enzymatic Activities during DNA Repair. Genes (Basel). 2021 Aug 25;12(9):1310.

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POLQ

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