Deficiencies in the recognition and repair of DNA damage in HGPS cells: Progeria causes chromatin disruptions, resulting in the formation of DSBs (double-strand breaks) and abnormal DDRs ( DNA damage response). Progerin can disrupt DDR pathways in HGPS cells. Accumulation of progerin causes disruption of the functions of some replication and repair factors, leading to mislocalization of the XPA protein at replication forks, replication fork stalling, and subsequently DNA DSBs. Binding of XPA to stalled hairpins overrides normal binding by repair proteins, leading to the accumulation of DSBs, which activates the ATM and ATR checkpoints and halts cell cycle progression. When mutant lamin proteins take over the immune system, they sequester replication and repair factors, leading to “stalled replication forks, which collapse into double-stranded DNA beaks (DSBs).” These DSBs bind to the Xeroderma pigmentosum group A (XPA) protein, which replaces the usual binding to DNA DSB repair proteins. This impaired binding may signal the activation of ATM and ATR, halting cell cycle progression, contributing to growth arrest. Instead of recruiting DSB repair proteins to DNA damage sites for repair as part of the damage response, Rad50/Rad51 nuclear foci did nothing. colocalize with γ-H2AX foci in HGPS cells. Although all other elements of the damage response system, such as the ATR and ATM checkpoints and Chk1 and Chk2, components critical for the repair of DNA DSBs and resting stalled replication forks, were not activated. Failure to recruit repair factors to sites of DNA damage causes irreparable DNA damage in HGPS cells. Binding of the Xeroderma pigmentosum group A (XPA) protein to DSBs generated by laminpathy played a role in the loss… halfway through the article. ..... absence of insulin receptor gene rearrangement, which could explain severe insulin resistance (ncbi.nlm.nih.gov). Works Cited Music R. Phillp and Zou Yue. (2009). Genomic instability and DNA damage responses in progeria resulting from defective maturation of prelamin A. Impact aging papers. Parreno, Justin and Cruz V. Alyssa. (2011). Accelerated aging in patients with Hutchinson-Gilford progeria syndrome: clinical signs, molecular causes, treatments, and insights into the aging process. UBCMJ.Pollex RL, Hegele RA. (2004). Hutchinson-Gilford progeria syndrome. Clinical genetics: Blackwell Munksgaard.Sarkar KP and Shinton A R. (2000). Hutchinson-Guilford progeria syndrome. Postgraduate Medical Journal.Vignolo M., Gherzi R., Bellini C., & Briata P. (1991). Insulin receptor gene expression is reduced in cells from a progeric patient. Pub Med. Governor.