BLOOM SYNDROME: EFFECT OF MISSENCE MUTATIONS AND OXIDATIVE STRESS ON BLM GENE

Sikander Ali, Zainab Masood* and Nimra Khan

ABSTRACT

Bloom syndrome is a pleiotropic genetic disorder that belongs to group of chromosomal breakage syndromes. It is due to changes in a single gene; BLM gene. The RecQ family DNA helicases Bloom syndrome protein (BLM) plays a key role in protecting the genome angainst deleterious changes. The RECQ helicase DNA is metabolically involved in many functions and is therefore related to the origins of common cellular phenotypes that are identified and defined for RECQ deficient cells. Pathologic mutations are involved in Bloom syndrome. BLM interacts with telomeric proteins and functions in telomere maintenance. Oxidative stress is ROS-induced oxidative injury which causes mitochondrial alternations and change cellular metabolism, the ratio of GSSG/GSH is considerably lowered in BS patient that makes them sensitive to oxidative stress as well as increase in ROS production. BS as compared to other diseases is caused by oxidative stress which is characterized by accumulation of cancer cells and degeneration of neurological cells. Many studies related to phenotype of BS have been done which not only explain its causes but also therapeutic strategies to combat this disease.

Keywords: DNA repair, RecQ helicase, genomic instability, replication, mutation, premature aging, cancer, Bloom Syndrome, telomere, oxidative stress.