TY - JOUR
T1 - Nucleotide excision repair disorders and the balance between cancer and aging
AU - Andressoo, Jaan Olle
AU - Hoeijmakers, Jan H.J.
AU - Mitchell, James R.
PY - 2006/12/15
Y1 - 2006/12/15
N2 - Cancer incidence increases with age and is driven by accumulation of mutations in the DNA. In many so-called premature aging disorders, cancer appears earlier and at elevated rates. These diseases are predominantly caused by genome instability and present with symptoms, including cancer, resembling "segments" of aging and are thus often referred to as "segmental progerias". Two related segmental progerias, Cockayne syndrome (CS) and trichothiodystrophy (TTD), don't fit this pattern. Although caused by defects in genome maintenance via the nucleotide excision DNA repair (NER) pathway and displaying severe progeroid symptoms, CS and TTD patients appear to lack any cancer predisposition. More strikingly, genetic defects in the same NER pathway, and in some cases even within the same gene, XPD, can also give rise to disorders with greatly elevated cancer rates but without progeria (xeroderma pigmentosum). In this review, we will discuss the connection between genome maintenance, aging and cancer in light of a new mouse model of XPD disease.
AB - Cancer incidence increases with age and is driven by accumulation of mutations in the DNA. In many so-called premature aging disorders, cancer appears earlier and at elevated rates. These diseases are predominantly caused by genome instability and present with symptoms, including cancer, resembling "segments" of aging and are thus often referred to as "segmental progerias". Two related segmental progerias, Cockayne syndrome (CS) and trichothiodystrophy (TTD), don't fit this pattern. Although caused by defects in genome maintenance via the nucleotide excision DNA repair (NER) pathway and displaying severe progeroid symptoms, CS and TTD patients appear to lack any cancer predisposition. More strikingly, genetic defects in the same NER pathway, and in some cases even within the same gene, XPD, can also give rise to disorders with greatly elevated cancer rates but without progeria (xeroderma pigmentosum). In this review, we will discuss the connection between genome maintenance, aging and cancer in light of a new mouse model of XPD disease.
KW - Aging
KW - Cancer
KW - Cockayne syndrome
KW - Insulin-like growth factor 1
KW - Nucleotide excision repair
KW - Xeroderma pigmentosum
UR - http://www.scopus.com/inward/record.url?scp=33845683300&partnerID=8YFLogxK
U2 - 10.4161/cc.5.24.3565
DO - 10.4161/cc.5.24.3565
M3 - Review article
C2 - 17172862
AN - SCOPUS:33845683300
SN - 1538-4101
VL - 5
SP - 2886
EP - 2888
JO - Cell Cycle
JF - Cell Cycle
IS - 24
ER -