DNA REPAIR PATHWAYS AND CANCER PREDISPOSITION

“𝔻ℕ𝔸 π•£π•–π•‘π•’π•šπ•£ π•šπ•€ π•₯𝕙𝕖 π•˜π•¦π•’π•£π••π•šπ•’π•Ÿ 𝕠𝕗 π•˜π•–π•Ÿπ• π•žπ•šπ•” π•šπ•Ÿπ•₯π•–π•˜π•£π•šπ•₯π•ͺ, π•’π•Ÿπ•• π•šπ•₯𝕀 π•—π•’π•šπ•π•¦π•£π•– π•šπ•€ 𝕒 π•—π•¦π•Ÿπ••π•’π•žπ•–π•Ÿπ•₯𝕒𝕝 𝕔𝕒𝕦𝕀𝕖 𝕠𝕗 π•”π•’π•Ÿπ•”π•–π•£.” - Tomas Lindahl (Nobel Laureate)

🧬 DNA serves as life’s blueprint, yet it is constantly assaulted by environmental insults (UV, radiation, chemical mutagens) and intrinsic stressors (replication errors, oxidative damage). To safeguard stability, cells rely on highly coordinated DNA repair pathways. When these mechanisms falter, mutations accumulate, elevating cancer risk.

          πŸ”Ή Key DNA Repair Pathways:

1. NER (Nucleotide Excision Repair): Removes bulky lesions (e.g., UV-induced adducts). Defects cause Xeroderma Pigmentosum, with extreme skin cancer risk.
2. BER (Base Excision Repair): Fixes oxidative and small base modifications.
3. HR (Homologous Recombination): Error-free repair of double-strand breaks using a template. Mutations in BRCA1/2 impair HR & predispose to breast/ovarian cancers.
4. NHEJ (Non-Homologous End Joining): Repairs breaks without a template, faster but error-prone; essential in non-dividing cells.
5. MMR (Mismatch Repair): Corrects replication errors. Mutations in MLH1, MSH2, MSH6, PMS2 drive Lynch syndrome, heightening colorectal or endometrial cancer risk.

          πŸ”Ή Cancer Predisposition:
Inherited mutations in repair genes severely increase risk. Examples:

BRCA1/2 → hereditary breast/ovarian cancer.

MMR genes → Lynch syndrome.

NER genes → Xeroderma Pigmentosum.

          πŸ”Ή Beyond inherited syndromes, somatic defects in repair pathways are pervasive in sporadic cancers, fueling genomic instability & tumorigenesis.

➡️ Clinical Implications:

Therapeutic Targeting: Tumors with HR deficiency (e.g., BRCA mutations) are sensitive to PARP inhibitors, leveraging synthetic lethality.

Precision Prevention: Genetic testing identifies at-risk individuals, guiding early screening, lifestyle modification, or prophylactic interventions.

⚠️ In an Oystershell, DNA repair pathways safeguard genomic stability. Their disruption is a central driver of cancer predisposition and progression. Advancing our understanding of these mechanisms not only sharpens cancer risk prediction but also enables development of targeted therapies & personalized prevention strategies; a critical step in transforming oncology.

Abubakar Abubakar ✍🏼

• Lindahl T, Wood RD. Quality control by DNA repair. Science. 1999; 286(5446):1897-905.

•  Jackson SP, Bartek J. The DNA-damage response in human biology & disease. Nature. 2009; 461:1071-1078.

• Lord CJ, Ashworth A. BRCAness revisited. Nat Rev Cancer. 2016; 16:110-120.

• Jiricny J. The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol. 2006; 7:335-346.

#DNARepair #CancerGenetics #CancerResearch #Oncology #BRCA #LynchSyndrome #MolecularBiology #HumanGenetics #PrecisionMedicine #Genomics #DNARepairPathways #CancerBiomarkers #CRISPR #Cas9 #PublicHealthπŸ”¬⚕️πŸŽ—️

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