Table 1.

Intrinsic and Extrinsic DNA-Damaging Agents, and the Types and Consequences of Associated DNA Damage

Source	Damaging Agent or Event		Major Form(s) of Damage	Primary Consequence on DNA Structure and Transactions
Intrinsic	spontaneous hydrolysis		uracil	little structural impact; causes C→T mutations
			AP sites	increased phosphodiester backbone flexibility, possible structural distortion; non-coding, mutagenic; polymerase block
	replication mistakes		mispair	some DNA conformational effects, depending on mispair; mutagenic
			indel	conformational effect (hairpin loop); MSI
	replicative stress		DSBs	fork collapse, genomic instability
	reactive endogenous chemicals	ROS	base modifications, AP sites, SSBs	depending on the damage, mutagenic or polymerase block (see text for examples)
		SAM	methylated bases, e.g., O6-methylguanine	little structural impact; causes G→A mutations
		aldehydes (e.g., malondialdehyde)	base adducts, ICLs	helix-distortion, covalent bridge; polymerase block; possible error-prone bypass
Extrinsic	radiation	UV	CPDs, 6-4PPs	helix-distorting; polymerase block; possible error-prone bypass
		IR	base modifications, SSBs and DSBs	depending on the damage, mutagenic or polymerase block; genomic instability
	environmental chemicals	B[a]P	base adduct	helix-distorting; polymerase block; possible G→T mutations
		AFB1	base adducts	helix-distortion; polymerase block; possible error-prone bypass
	chemotherapeutic agents	cisplatin	base adducts, intra and interstrand crosslinks	helix-distortion; polymerase block
		etoposide, doxorubicin	DSBs, protein-DNA adduct	replication and transcription block