DNA Repair Deficiency Associated with Hematological Neoplasms

The genome of living organisms is constantly subjected to conditions that induce damage to DNA.A wide variety of DNA lesions are produced either as the result of normal metabolic processes or exogenous sources (ionizing radiation, UV light) (Seviour and Lin 2010).This damage to genomic material represents a persistent threat to genomic stability.Mammalian cells have developed a range of molecular mechanisms capable of responding to DNA damage.These mechanisms include activation of DNA damage repair pathways or tolerance systems, initiation of complex regulatory networks that coordinate cell cycle progression and repair and induction of apoptosis if errors are detected (Madhusudan and Middleton 2005).At a cellular level, if a DNA lesion is misrepaired, it can lead to genomic instability.It is therefore essential for a cell to efficiently respond to DNA damage.Different DNA Repair Mechanisms exist and play a major role in restoring genomic integrity.These include: The Direct Repair Pathway (DR), Base Excision Repair Mechanism (BER), Nucleotide Excision Repair Pathway (NER), Non-Homologous End Joining (NHEJ), Homologous Recombination (HR) and DNA Mismatch Repair Pathway (MMR).It is quite obvious that any defect in these mechanisms can lead to improperly repaired DNA lesions and genomic abnormalities, which constitute the hallmark of tumorigenesis (Cline and Hanawalt 2003, Hwang et al. 1999).Indeed, mutations and polymorphisms of DNA repair genes have been correlated with different hereditary and sporadic cancer types (Altieri et al. 2008).Hematological malignancies account for about 8% of all cancers in men and 6% of all cancers in women.There is a considerable body of evidence that suggests a strong association between DNA repair deficiency and hematological malignancies.This article is meant to serve as an overview of the relevant literature focusing on mutations and polymorphisms of DNA repair genes that predispose to certain hematological malignancies.We also discuss how defects in DNA repair affect sensitivity to chemotherapy. DNA repair mechanismsBelow, we briefly summarize our current knowledge regarding DNA Repair Mechanisms.www.intechopen.